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Sample records for b16 melanoma transplant

  1. Growth Inhibition of Re-Challenge B16 Melanoma Transplant by Conjugates of Melanogenesis Substrate and Magnetite Nanoparticles as the Basis for Developing Melanoma-Targeted Chemo-Thermo-Immunotherapy

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    Tomoaki Takada

    2009-01-01

    Full Text Available Melanogenesis substrate, N-propionyl-cysteaminylphenol (NPrCAP, is selectively incorporated into melanoma cells and inhibits their growth by producing cytotoxic free radicals. Magnetite nanoparticles also disintegrate cancer cells and generate heat shock protein (HSP upon exposure to an alternating magnetic field (AMF. This study tested if a chemo-thermo-immunotherapy (CTI therapy strategy can be developed for better management of melanoma by conjugating NPrCAP on the surface of magnetite nanoparticles (NPrCAP/M. We examined the feasibility of this approach in B16 mouse melanoma and evaluated the impact of exposure temperature, frequency, and interval on the inhibition of re-challenged melanoma growth. The therapeutic protocol against the primary transplanted tumor with or without AMF exposure once a day every other day for a total of three treatments not only inhibited the growth of the primary transplant but also prevented the growth of the secondary, re-challenge transplant. The heat-generated therapeutic effect was more significant at a temperature of 43∘C than either 41∘C or 46∘C. NPrCAP/M with AMF exposure, instead of control magnetite alone or without AMF exposure, resulted in the most significant growth inhibition of the re-challenge tumor and increased the life span of the mice. HSP70 production was greatest at 43∘C compared to that with 41∘C or 46∘C. CD+T cells were infiltrated at the site of the re-challenge melanoma transplant.

  2. Oxidative burst of neutrophils against melanoma B16-F10.

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    Zivkovic, Morana; Poljak-Blazi, Marija; Zarkovic, Kamelija; Mihaljevic, Danijela; Schaur, Rudolf Joerg; Zarkovic, Neven

    2007-02-01

    Intensive oxidative burst was determined by chemiluminescence of peripheral blood neutrophils of mice that were intramuscularly injected with melanoma B16-F10 and/or subcutaneously with Sephadex G-200. The neutrophils from papula developed at the site of Sephadex injection were cytotoxic for the B16-F10 cells in vitro. However, survival of Sephadex injected tumour-bearing mice was lower than of control animals bearing B16-F10, while their tumours grew faster and were less necrotic. Thus, it is likely that injection of Sephadex distracted the neutrophils from the tumour allowing faster progression of the tumour, indicating that neutrophils may have an important role in the host defence against malignant cells in the early stage of tumour development. PMID:16564616

  3. Effects of ultraviolet irradiation on cultured B-16 melanoma cells

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    Changes of the plasma membrane during exposure to ultraviolet light were studied in cultured B-16 melanoma cells by the method of electron spin resonance with the spin labelling technique. The lipid peroxide content increased immediately after exposure to UV light and returned to the normal level, 3 hrs post-exposure. Plasma membrane fluidity increased significantly, 3 - 6 hrs after exposure, and remained at the increased level in the hydrophobic region of the membrane until 18 hrs. There were no significant differences in phospholipid content before and after exposure, except for cardiolipin. (author)

  4. Stimulation of melanogenesis by scoparone in B16 melanoma cells

    Institute of Scientific and Technical Information of China (English)

    Jeong-yeh YANG; Jeung-hyun KOO; Young-gil SONG; Kang-beom KWON; Ju-hyung LEE; Hee-sook SOHN; Byung-hyun PARK; Eun-chung JHEE; Jin-woo PARK

    2006-01-01

    Aim: The effect of coumarin derivatives on melanogenesis was investigated in B16 murine melanoma cells. Methods: Melanin content and tyrosinase activity were analyzed spectrophotometrically. The expression of tyrosinase, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) were measured either by reverse transcription-polymerase chain reaction (RT-PCR) or Western blot. Results: Among the coumarin derivatives studied, scoparone (6,7-dimethoxycoumarin) was the most potent; the 6- or 7-methoxy group was found to be essential for the stimulation of melanogenesis. The melanin content was greatly increased by scoparone in a dose-dependent manner; there was no cytotoxicity at the effective concentrations. Scoparone increased enzyme activity as well as protein and mRNA expression of tyrosinase. In addition, mRNA of TRP-1 and TRP-2 were also increased after treatment with scoparone. H-89, an inhibitor of protein kinase A (PKA), completely inhibited the scoparone-induced increase of melanogenesis and the tyrosinase protein. Conclusion: These results suggest that scoparone-induced stimulation of melanogenesis is likely to occur at the transcriptional level of melanogenesis-related enzymes through PKA signaling.

  5. Effect of selenium compounds on murine B16 melanoma cells and pigmented cloned pB16 cells

    International Nuclear Information System (INIS)

    The effects of selenium compounds such as sodium selenite, sodium selenate, seleno-DL-cystine and seleno-DL-methionine (100 μM and 10 μM) on B16 and pigmented cloned pB 16 murine melanoma cells were investigated in vitro. At the tested concentrations, B16 cells showed a greater sensitivity to the toxic effects of sodium selenite and seleno-DL-cystine than pB 16 cells, whereas no decrease of B 16 and pB 16 cell number was observed after incubation with sodium selenate or seleno-DL-methionine. Glutathione (GSH) percentages were strongly decreased only by selenite and seleno-DL-cystine; it was marked more in B 16 than in pB 16 cells. The pretreatment of B 16 cells with a GSH depleting agent (10 μM buthionine-[S,R]-sulfoximine) did not significantly influence the cytotoxic effects of selenite and seleno-DL-cystine. On both cell populations. GSH preincubation (50 μM) enhanced the cytotoxicity of selenite whereas the survival of seleno-DL-cystine treated cells was increased. Glutathione peroxidase (GSH-Px) activity in B 16 cells was more sensitive than in pB 16 cells to the activating effect of selenite, and particularly of seleno-DL-cystine; however, cell-free controls indicated that activation was mainly due to glutathione reductase. The rate of 75Se (as sodium selenite) uptake in both cell populations was maximal within the first hour of incubation, with a preferential accumulation in the cytosol; after 24 h of incubation, the amount of 75Se in cytosol and pellet was approximately the same. Gel filtration chromatography of lysed cells after incubation for 6 h with 10 μM 75Se-selenite showed that the radioactivity was eluted as two peaks corresponding to low (4-9 kDa) and high (280-320 kDa) molecular weights. Possible toxicological mechanisms are discussed at molecular level. (orig./MG)

  6. The effects of Hominis Placenta extract on Melanin synthesis of B16 melanoma cells

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    Hyung-Sik Seo

    2006-01-01

    Objective : This research was carried out for the development of medicine for vitiligo treatment and focused on the effect of Hominis Placenta extract on Melanin synthesis of B16 melanoma cells. Methods : Acitivity of tyrosinase playing a vital role in synthesis of Melanin and the quantity of Melanin, which is the final product in cultured B16 melanoma cells, effects of Hominis Placenta extract were measured. Results : The results indicated that Hominis Placenta extract increased both t...

  7. 5-Azacytidine and 5-aza-2'-deoxycytidine behave as different antineoplastic agents in B16 melanoma.

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    Cortvrindt, R.; Bernheim, J.; Buyssens, N.; Roobol, K.

    1987-01-01

    The antiproliferative effects of 5-azacytidine (acaCyd) and 5-aza-2'-deoxycytidine (azadCyd) were studied in murine B16 melanoma and a series of B16 melanoma derived mutant strains with selective resistances to the respective drugs. The in vitro cytotoxicities of azaCyd and azadCyd on B16 wild type, expressed in terms of IC50 values, were found to be 5 microM and 0.2 microM, respectively. The in vitro cytotoxicity of both drugs was dependent on the duration of exposure. Uridine and cytidine w...

  8. The Inhibitory Effect of Endostatin and Doxycycline Administration on B16 Melanoma Angiogenesis and Cellular Proliferation

    Institute of Scientific and Technical Information of China (English)

    Lisha Qi; Shiwu Zhang; Danfang Zhang; Xiaojin Yin; Sen Wang; Baochun Sun

    2008-01-01

    OBJECTIVE To investigate the effect of endostatin and doxycycline on melanoma cellular proliferation and tumor angiogenesis.METHODS The effects of endostatin and doxvcycline were studied in mice transplanted with B16 melanoma cells.The mice were divided into 4 groups that were trea ted as follows:endostatin treatment(E group),doxycycline treatment(D group),endostatin plus doxycycline trearment(DE group),controls(C group)received no treatment.Following 9 days of treatment the tumor tissue was removed to compare the differences in the tumor necrotic rate and micro-vessel density (MVD)among the different groups.Immunohistochemical staining was conducted to detect the expression of proliferating cell nuclear antigen(PCNA)in the different groups.RESULTS The MVD of the 3 experimental groups was significantly less than the control group,(F=10.888,P<0.05),indicating that doxycycline and endostatin can inhibit tumor angiogenesis by decreasing the tumor blood supply.This effect results in inhibition of tumor cellular proliferation and promotion of tumor cell necrosis.The tumor cell necrotic ra te of the 3 experimental groups were all significantly higher than the C group(F=7.229,P<0.05)and the difference between the DE and C groups also was statistically significant.PCNA expression in all 3 experimental groups was statistically less than the C group(F=17.729,P<0.05).CONCLUSION The combined use of endostatin and doxycyCline in vivo can influence PCNA exDression and angiogenesis in melanoma,and significantly inhibit melanoma cellular proliferation.

  9. Effect of Chlorogenic Acid on Melanogenesis of B16 Melanoma Cells

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    Hao-Rong Li

    2014-08-01

    Full Text Available Chlorogenic acid (CGA, the ester formed between caffeic acid and l-quinic acid, is a widespread phenolic compound. It is part of the human diet, found in foods such as coffee, apples, pears, etc. CGA is also was widely used in cosmetics, but the effects of CGA on melanogenesis are unknown. In this study, we analyzed the effects of CGA on cell proliferation, melanin content and tyrosinase of B16 murine melanoma cells. Additionally, the enzymatic reactions of CGA in B16 melanoma cells lytic solution were detected by UV spectrophotometry. Results showed CGA at 30 and 60 μM significantly suppresses cell proliferation. 8-MOP at 100 μM significantly promotes cell proliferation, but CGA can counter this. Incubated for 24 h, CGA (500 μM improves melanogenesis while suppressing tyrosinase activity in B16 melanoma cells or 8-methoxypsoralen (8-MOP co-incubated B16 melanoma cells. After 12 h, B16 melanoma cell treatment with CGA leads to an increase in melanin accumulation, however, after 48 h there is a decrease in melanin production which correlates broadly with a decrease in tyrosinase activity. CGA incubated with lytic solution 24 h turned brown at 37 °C. The formation of new products (with a maximum absorption at 295 nm is associated with reduction of CGA (maximum absorption at 326 nm. Therefore, CGA has its two sidesroles in melanogenesis of B16 melanoma cells. CGA is a likely a substrate of melanin, but the metabolic product(s of CGA may suppress melanogenesis in B16 melanoma cells by inhibiting tyrosinase activity.

  10. Fluvastatin increases tyrosinase synthesis induced by UVB irradiation of B16F10 melanoma cells.

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    Krzysztof Włodarski

    2010-02-01

    Full Text Available Statins are widely used to lower plasma concentrations of lipids, e.g. cholesterol. One of the main effects of statin treatment is inhibition of hydroxymethyl glutaryl-coenzyme A reductase. The role of fluvastatin, a frequently used statin, was examined in potential modulation of tyrosinase (key enzyme of melanogenesis synthesis. Levels of tyrosinase mRNA induced by UVB irradiation of B16F10 melanoma cell line were measured by real time PCR. Fluvastatin increases tyrosinase mRNA production induced by UVB irradiation in B16F10 melanoma cell line. Fluvastatin treatment may potentially influence melanin synthesis and protection against UV irradiation.

  11. Fluvastatin increases tyrosinase synthesis induced by UVB irradiation of B16F10 melanoma cells

    International Nuclear Information System (INIS)

    Statins are widely used to lower plasma concentrations of lipids, e.g. cholesterol. One of the main effects of statin treatment is inhibition of hydroxymethyl glutaryl-coenzyme A reductase. The role of fluvastatin, a frequently used statin, was examined in potential modulation of tyrosinase (key enzyme of melanogenesis) synthesis. Levels of tyrosinase mRNA induced by UVB irradiation of B16F10 melanoma cell line were measured by real time PCR. Fluvastatin increases tyrosinase mRNA production induced by UVB irradiation in B16F10 melanoma cell line. Fluvastatin treatment may potentially influence melanin synthesis and protection against UV irradiation. (authors)

  12. Antiproliferative effect of the jararhagin toxin on B16F10 murine melanoma

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    Maria, Durvanei Augusto; da Silva, Manuela Garcia Laveli; Correia, Mario Cesar; Ruiz, Itamar Romano Garcia

    2014-01-01

    Background Malignant melanoma is a less common but highly dangerous form of skin cancer; it starts in the melanocytes cells found in the outer layer of the skin. Jararhagin toxin, a metalloproteinase isolated from Bothrops jararaca snake venom acts upon several biological processes, as inflammation, pain, platelet aggregation, proliferation and apoptosis, though not yet approved for use, may one day be employed to treat tumors. Methods B16F10 murine melanoma cells were treated with jararhagin...

  13. Combination of amino acids reduces pigmentation in B16F0 melanoma cells.

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    Ishikawa, Masago; Kawase, Ichiro; Ishii, Fumio

    2007-04-01

    Amino acids, the building blocks of proteins, play significant roles in numerous physiological events in mammals. As the effects of amino acids on melanogenesis have yet to be demonstrated, the present study was conducted to identify whether amino acids, in particular alanine, glycine, isoleucine and leucine, influence melanogenesis in B16F0 melanoma cells. Glycine and L-isoleucine, but not D-isoleucine, reduced melanogenesis in a concentration-dependent manner without any morphological changes in B16F0 melanoma cells. L-Alanine and L-leucine, but not D-alanine and D-leucine, also reduced melanogenesis without any morphological changes in B16F0 melanoma cells. However these amino acids did not show a concentration-dependency. Combination of L-alanine and the other amino acids, particularly 4 amino acids combination, had an additive effect on the inhibition of melanogenesis compared with single treatment of L-alanine. None of the amino acids affected the activity of tyrosinase, a key enzyme in melanogenesis. These results suggest that L-alanine, glycine, L-isoleucine and L-leucine, but not the D-form amino acids, have a hypopigmenting effect in B16F0 melanoma cells, and that these effects are not due to the inhibition of tyrosinase activity. Combination of these 4 amino acids had the additive effect on hypopigmentation that was as similar as that of kojic acid. PMID:17409501

  14. Difference in 3H-thymidine incorporation after irradiation between murine B16 melanoma and squamous cell carcinoma in vivo

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    The tumor growth and cell proliferation kinetics of B16 melanoma and transplantable squamous cell carcinoma (BSC tumor) in C57BL/6 mice were studied after single-dose X-ray and fast-neutron (2 MeV) irradiations. From tumor volume change studies, B16 tumor showed a high relative biological effectiveness (RBE) value (5.5) compared to that of BSC tumor (3.5). The tissue characteristics of the two tumors were not significantly different, but the post-irradiation changes in mitotic index (MI) and lebeling index (LI) were dependent on the tumor and on the nature of the radiation. After irradation, mitosis was immediately inhibited (G2 block) but recovered within several hours in BSC and X-ray-irradiated B16 tumors. The neutron-irradiated B16 tumors showed no recovery up to the end of the observation period. After X-ray irradiation, of B16 tumors, LI showed an Fimmediate reduction, while the reduction was delayed several hours (equal to G1 + M) in BSC tumors. The extent of reduction was dose-dependent, and its recovery was coincident with the recovery of mitosis. The change in LI of neutron-irradiated BSC tumors was similar to that with X-rays, but no change in LI was observed in neutron-irradiated B16 tumors over 18 hr. From these results, it is assumed that the cell progression of B16 tumors is susceptible to ionizing radiation, and that G1 block is induced as a result of irradiation. (author)

  15. Mechanisms regulating c-met overexpression in liver-metastatic B16-LS9 melanoma cells.

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    Elia, G; Ren, Y; Lorenzoni, P; Zarnegar, R; Burger, M M; Rusciano, D

    2001-01-01

    Liver selected B16-LS9 melanoma cells show a dramatic overexpression of the proto-oncogene c-met, the cellular receptor for hepatocyte growth factor/scatter factor. As a consequence, c-met becomes constitutively active, and the cells become more responsive to hepatocyte growth factor stimulation. We have investigated the molecular mechanisms regulating c-met expression in both the parental line B16-F1, which has low expression levels, and the liver-specific B16-LS9, overexpressing c-met. Overexpression is observed at the protein and mRNA levels, however without further evidence of gene amplification or rearrangement. c-met promoter activity was higher in B16-LS9 than B16-F1 cells, and also a nuclear run-off showed higher transcription levels in B16-LS9 cells. Moreover, we found that c-met mRNA had a longer half-life in B16-LS9 cells, thus indicating also the involvement of post-transcriptional regulation mechanisms. Finally, we found evidence that autonomous activation of the melanocortin receptor-1 (MCR-1) is at least partially responsible for c-met upregulation in B16-LS9 cells, since treatment of the cells with a potent MSH antagonist (the agouti peptide) has strong down-regulatory effects. PMID:11255230

  16. 5-Azacytidine and 5-aza-2'-deoxycytidine behave as different antineoplastic agents in B16 melanoma.

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    Cortvrindt, R.; Bernheim, J.; Buyssens, N.; Roobol, K.

    1987-01-01

    The antiproliferative effects of 5-azacytidine (acaCyd) and 5-aza-2'-deoxycytidine (azadCyd) were studied in murine B16 melanoma and a series of B16 melanoma derived mutant strains with selective resistances to the respective drugs. The in vitro cytotoxicities of azaCyd and azadCyd on B16 wild type, expressed in terms of IC50 values, were found to be 5 microM and 0.2 microM, respectively. The in vitro cytotoxicity of both drugs was dependent on the duration of exposure. Uridine and cytidine were able to reverse the in vitro cytotoxicity of azaCyd, but not of azadCyd. Conversely, 2'-deoxycytidine was able to reverse the cytotoxic effect of azadCyd but not of azaCyd. Thymidine and 2'-deoxyuridine had no detectable effects on the in vitro cytotoxicity of either azaCyd or azadCyd. B16 melanoma mutant strains that were selected for resistance to azaCyd showed no cross-resistance to azadCyd, cytosine arabinoside or the fluorinated pyrimidine analogues FUrd, FCyd, FdUrd and FdCyd. Mutant strains that were selected for resistance to azadCyd showed no cross-resistance to azaCyd or fluorinated pyrimidine analogs, but only to cytosine arabinoside. The combined data suggest that azaCyd and azadCyd follow different routes of intracellular metabolic activation and exert their cytotoxic activity via different intracellular targets. PMID:2444244

  17. Sox10 controls migration of B16F10 melanoma cells through multiple regulatory target genes.

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    Ikjoo Seong

    Full Text Available It is believed that the inherent differentiation program of melanocytes during embryogenesis predisposes melanoma cells to high frequency of metastasis. Sox10, a transcription factor expressed in neural crest stem cells and a subset of progeny lineages, plays a key role in the development of melanocytes. We show that B16F10 melanoma cells transfected with siRNAs specific for Sox10 display reduced migratory activity which in turn indicated that a subset of transcriptional regulatory target genes of Sox10 is likely to be involved in migration and metastasis of melanoma cells. We carried out a microarray-based gene expression profiling using a Sox10-specific siRNA to identify relevant regulatory targets and found that multiple genes including melanocortin-1 receptor (Mc1r partake in the regulation of migration. We provide evidences that the effect of Sox10 on migration is mediated in large part by Mitf, a transcription factor downstream to Sox10. Among the mouse melanoma cell lines examined, however, only B16F10 showed robust down-regulation of Sox10 and inhibition of cell migration indicating that further dissection of dosage effects and/or cell line-specific regulatory networks is necessary. The involvement of Mc1r in migration was studied in detail in vivo using a murine metastasis model. Specifically, B16F10 melanoma cells treated with a specific siRNA showed reduced tendency in metastasizing to and colonizing the lung after being injected in the tail vein. These data reveal a cadre of novel regulators and mediators involved in migration and metastasis of melanoma cells that represents potential targets of therapeutic intervention.

  18. Electrochemotherapy by pulsed electromagnetic field treatment (PEMF) in mouse melanoma B16F10 in vivo

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    Kranjc Simona; Kranjc Matej; Scancar Janez; Jelenc Jure; Sersa Gregor; Miklavcic Damijan

    2016-01-01

    Introduction Pulsed electromagnetic field (PEMF) induces pulsed electric field, which presumably increases membrane permeabilization of the exposed cells, similar to the conventional electroporation. Thus, contactless PEMF could represent a promising approach for drug delivery. Materials and methods Noninvasive electroporation was performed by magnetic field pulse generator connected to an applicator consisting of round coil. Subcutaneous mouse B16F10 melanoma tumors were treated with intrave...

  19. [6]-Shogaol inhibits melanogenesis in B16 mouse melanoma cells through activation of the ERK pathway

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    Yao, Cheng; Oh, Jang-Hee; Oh, Inn Gyung; Park, Chi-Hyun; Chung, Jin Ho

    2012-01-01

    Aim: To investigate the effect of [6]-shogaol, an active ingredient in ginger, on melanogenesis and the underlying mechanisms. Methods: B16F10 mouse melanoma cells were tested. Cell viability was determined with the MTT assay. Melanin content and tyrosinase activity were analyzed with a spectrophotometer. The protein expression of tyrosinase and microphthalmia associated transcription factor (MITF), as well as phosphorylated or total ERK1/2 and Akt were measured using Western blot. Results: T...

  20. Superoxide dismutase activity as a function of culture aging of B-16 mouse melanoma cells

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    JOVANA B. SIMIC-KRSTIC

    2004-12-01

    Full Text Available The C3 clone of B-16 mouse melanoma was cultured for 1, 6 and 9 days and analysed. The changes which are not directly linked to melanogenesis in the B-16 / C3 cultures during their maturation were characterized. Early (1 day, confluent (6 days and old (9 days cell cultures are distinguished by their leucine aminopeptidase (LAP and a-naphthyl acetate esterase (ANAE isoenzyme patterns. Both quantitative and qualitative changes in LAP and ANAE isoenzyme can be observed during culture maturation. There is an increase in the activity of the enzyme copper, zinc-containing superoxide-dismutase (CuZn SOD. The increaase in the CuZn SOD enzyme activity might be related to B-16/C3 cell melanogenesis and / or to differentiation.

  1. Depigmenting Effect of Kojic Acid Esters in Hyperpigmented B16F1 Melanoma Cells

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    Ahmad Firdaus B. Lajis

    2012-01-01

    Full Text Available The depigmenting effect of kojic acid esters synthesized by the esterification of kojic acid using Rhizomucor miehei immobilized lipase was investigated in B16F1 melanoma cells. The depigmenting effect of kojic acid and kojic acid esters was evaluated by the inhibitory effect of melanin formation and tyrosinase activity on alpha-stimulating hormone- (α-MSH- induced melanin synthesis in B16F1 melanoma cells. The cellular tyrosinase inhibitory effect of kojic acid monooleate, kojic acid monolaurate, and kojic acid monopalmitate was found similar to kojic acid at nontoxic doses ranging from 1.95 to 62.5 μg/mL. However, kojic acid monopalmitate gave slightly higher inhibition to melanin formation compared to other inhibitors at doses ranging from 15.63 to 62.5 μg/mL. Kojic acid and kojic acid esters also show antioxidant activity that will enhance the depigmenting effect. The cytotoxicity of kojic acid esters in B16F1 melanoma cells was significantly lower than kojic acid at high doses, ranging from 125 and 500 μg/mL. Since kojic acid esters have lower cytotoxic effect than kojic acid, it is suggested that kojic acid esters can be used as alternatives for a safe skin whitening agent and potential depigmenting agents to treat hyperpigmentation.

  2. Inhibitory effect of cordycepin on experimental hepatic metastasis of B16-F0 mouse melanoma cells.

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    Sato, Ayuko; Yoshikawa, Noriko; Kubo, Erika; Kakuda, Mami; Nishiuchi, Arisa; Kimoto, Yoko; Takahashi, Yuta; Kagota, Satomi; Shinozuka, Kazumasa; Nakamura, Kazuki

    2013-01-01

    In a previous study performed by our group, we demonstrated that the water extract of Cordyceps sinensis (WECS) significantly prevented tumor metastasis from the spleen to the liver, using B16-F0 mouse melanoma cells as a model. In this study, we investigated the anti-metastatic activity of cordycepin (3'-deoxyadenosine), one of the components of WECS, using an identical model of mice injected with B16-F0 cells into the spleen. All mice inoculated with B16-F0 cells died due to liver metastases via the portal vein from the spleen. Control mice not administered cordycepin exhibited higher serum levels of alanine aminotransferase (ALT) due to damage to the liver by metastasized B16-F0 cells from the spleen, and survival times ranged from 17 to 22 days after tumor inoculation. Cordycepin was intraperitoneally administered to mice, and resulted in significantly lower serum ALT levels and longer survival times than those observed in control mice. Taken together, these results indicate that cordycepin may be the active ingredient in C. sinensis exerting an anti-metastatic effect, and may be a potential candidate anti-metastatic agent. PMID:24292575

  3. DMEM enhances tyrosinase activity in B16 mouse melanoma cells and human melanocytes

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    Panpen Diawpanich

    2008-07-01

    Full Text Available Media components may affect the activities of cultured cells. In this study, tyrosinase activity was evaluated by using B16-F10 mouse melanoma cell lines (B16-F10 and primary human melanocytes cultured in different media. An optical density measurement and a L-dopa reaction assay were used as the determination of the tyrosinase activity. The study of B16-F10 found the optical density to be 2010, 2246 and 2961 in cells cultured in RPMI Medium 1640 (RPMI1640,Minimum Essential Medium (MEM and Dulbecco’s Modified Eagle Medium (DMEM, respectively. Moreover, compared to RPMI 1640 and MEM, DMEM showed the darkest color of melanin formation in culture media and in cells after the L-dopa reaction assay. Addition of kojic acid showed a significant inhibitory effect on tyrosinase activity in all media.Whereas MCDB153 showed no significant effect on human melanocytes, DMEM caused a dramatic increase in tyrosinase activity after 4 days of cultivation. Addition of kojic acid showed a significant tyrosinase inhibitory effect in DMEM only. Furthermore, an active ingredient in green tea, epigallocathechin gallate (EGCG could inhibit tyrosinase activity in both B16-F10 and human melanocytes cultured in DMEM. In summary, these results suggest that DMEM is a suitable medium that provides high detection sensitivity in a tyrosinase inhibition assay.

  4. Melanogenesis Inhibitory Activity of Two Generic Drugs: Cinnarizine and Trazodone in Mouse B16 Melanoma Cells

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    Te-Sheng Chang

    2011-12-01

    Full Text Available More than 200 generic drugs were screened to identify the inhibitory activity on melanogenesis in mouse B16 melanoma cells. Cinnarizine and trazodone were identified as melanogenesis inhibitors. The inhibitory effects of the two drugs on cell survival, melanogenesis, and tyrosinase activity were investigated. The results showed that both cinnarizine and trazodone inhibited melanogenesis in B16 cells by a dose-dependent manner at the non-cytotoxic concentrations. Based on the results of the present study, seeking new melanogenesis inhibitors from generic drugs is an alternative approach to developing new depigmenting agents in cosmeceuticals. Moreover, cinnarizine and trazodone were proven to be good candidates as skin-whitening agents for treatment of skin hyperpigmentation.

  5. The effect of antineoplastic drug NSC631570 on immunogenicity of B16 melanoma

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    Larysa M.Skivka

    2014-06-01

    Full Text Available Objectives: NSC631570 is a cytotoxic drug with the ability to be selectively accumulated in tumor tissue and activate apoptosis only in malignant cells and not in normal cells. Therapy with NSC631570 is accompanied by the stimulation of anticancer immune responses. It is known that cytotoxic anticancer drugs have additional effects on the immune system of tumor-bearing organism by increasing the immunogenic properties of tumor cells. This study aimed to investigate the immunogenicity of melanoma B16 after treatment with NSC631570. Methods: Two melanoma B16 sublines with different metastatic potentials were used. For in vivo growth cells were inoculated intravenously into C57BL/6 mice. The anticancer effect was calculated according to the growth inhibition index. Cell viability was determined by the MTT test. Cell apoptosis and necrosis were assessed by flow cytometry. HMGB1 expression, the serum level of cytokines and cytokine profile in tumor tissue were determined by ELISA. TAP1 and TAP2 expression was evaluated in RT-PCR and by Western blot. Results: Treatment of melanoma B16 cells with NSC631570 at apoptogenic concentrations induced tumor cell death accompanied by dose-dependent HMGB1 release in vitro. At the non-apoptogenic concentration the preparation caused an increase in TAP expression. The therapeutic efficacy of NSC631570 was also associated with strong release of HMGB1 in the serum of tumor-bearing mice and was more expressed in the case of the high-metastatic tumor variant. The therapeutic effect was accompanied by an increase of levels of Th1 cytokines in the serum and in tumor tissue of treated animals. Conclusion: In addition to the direct induction of tumor cell apoptosis, the preparation can increase the tumor immunogenicity. [J Exp Integr Med 2014; 4(2.000: 93-105

  6. Differential radiosensitivity in cultured B-16 melanoma cells following interrupted melanogenesis induced by glucosamine

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    Mileo, A.M.; Mattei, E.; Fanuele, M.; Delpino, A.; Ferrini, U. (Regina Elena Cancer Institute, Rome (Italy))

    1989-05-01

    The relationship between cell pigmentation and radiosensitivity was investigated in a cell model in which melanogenesis was suppressed by a glycosylation inhibitor. It was found that X-irradiation of melanotic B-16 melanoma cells and their amelanotic counterparts, obtained by glucosamine treatment, showed an inverse correlation between radiosensitivity and melanin contents. Since melanogenesis interruption by glucosamine does not affect the DNA repair capacity of nonpigmented cells, it is likely that intracellular melanins play a role in the relative resistance of pigmented cells to X-irradiation.

  7. Differential radiosensitivity in cultured B-16 melanoma cells following interrupted melanogenesis induced by glucosamine

    International Nuclear Information System (INIS)

    The relationship between cell pigmentation and radiosensitivity was investigated in a cell model in which melanogenesis was suppressed by a glycosylation inhibitor. It was found that X-irradiation of melanotic B-16 melanoma cells and their amelanotic counterparts, obtained by glucosamine treatment, showed an inverse correlation between radiosensitivity and melanin contents. Since melanogenesis interruption by glucosamine does not affect the DNA repair capacity of nonpigmented cells, it is likely that intracellular melanins play a role in the relative resistance of pigmented cells to X-irradiation

  8. Depigmenting mechanism of NSAIDs on B16F1 melanoma cells

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    Sato, Kazuomi; Takahashi, Hideki; Toriyama, Masaru

    2011-01-01

    The aim of the present work was to clarify the anti-melanogenic mechanism of non-steroidal anti-inflammatory drugs (NSAIDs). Mefenamic acid, diclofenac, and nimesulide were used in this study, and these drugs inhibit melanin synthesis in B16F1 melanoma cells. To elucidate the anti-melanogenic mechanism of NSAIDs, we performed western blotting analysis for melanogenic proteins, such as tyrosinase, TRP-1, and TRP-2. All NSAIDs used in this study inhibited tyrosinase protein level. Semi-quantita...

  9. Evaluation of Depigmenting Activity by 8-Hydroxydaidzein in Mouse B16 Melanoma Cells and Human Volunteers

    OpenAIRE

    Ching-Gong Lin; Mon-Han Wu; Te-Sheng Chang; Sorgan Shou-Ku Tai

    2009-01-01

    In our previous study, 8-hydroxydaidzein (8-OHDe) was demonstrated to be a potent and unique suicide substrate of mushroom tyrosinase. In this study, the compound was evaluated for in vitro cellular tyrosinase and melanogenesis inhibitory activities in mouse B16 melanoma cells and for in vivo skin-whitening activity in human volunteers. Tyrosinase activity and melanogenesis in the cell culture incubated with 10 µM of 8-OHDe were decreased to 20.1% and 51.8% of control, respectively, while no ...

  10. Antineoplastic effects of Rhodiola crenulata treatment on B16-F10 melanoma.

    Science.gov (United States)

    Dudek, Maxine C; Wong, Kaitlyn E; Bassa, Lotfi M; Mora, Maria Carmen; Ser-Dolansky, Jennifer; Henneberry, Jean M; Crisi, Giovanna M; Arenas, Richard B; Schneider, Sallie S

    2015-12-01

    Melanoma is an aggressive form of skin cancer with limited treatment options for advanced stage disease. Early detection and wide surgical excision remain the initial mode of treatment for primary tumors thus preventing metastases and leading to improved prognosis. Through this work, we have evaluated the antineoplastic effects of Rhodiola crenulata (R. crenulata) root extracts on the B16-F10 melanoma cell line, both in vitro and in vivo. We observed that R. crenulata treatment resulted in increased cell death as well as a reduction in tumor cell proliferation and migration in vitro. Additionally, we observed that R. crenulata decreased the expression of integrin β1 and vimentin and increased the expression of E-cadherin. Further, in mice treated with a topical R. crenulata-based cream therapy, tumors were more likely to have a radial growth pattern, a reduction in mitotic activity, and an increase in tumor necrosis. We also observed that mice drinking water supplemented with R. crenulata displayed a reduction of metastatic foci in disseminated models of melanoma. Collectively, these findings suggest that R. crenulata exhibits striking antitumorigenic and antimetastatic properties and that this extract may harbor potential novel adjuvant therapy for the treatment of melanoma. PMID:26159852

  11. Human placental lipid induces mitogenesis and melanogenesis in B16F10 melanoma cells

    Indian Academy of Sciences (India)

    Shampa Mallick; Samir Kumar Mandal; Ranjan Bhadra

    2002-06-01

    A hydroalcoholic extract of fresh term human placenta was found to be mitogenic as well as melanogenic on B16F10 mouse melanoma in an in vitro culture. The extract, a reservoir of a large number of bioactive molecules, was resolved to get the lipid fraction. Its activity was evaluated on B16F10 mouse melanoma by assessing the change in cellular morphology, growth and melanin induction. The lipid fraction, placental total lipid fraction (PTLF) tested in the study employed doses of 0.01 to 200 g/ml; optimum growth and melanization accompanied by morphological changes were recorded at 10 and 100 g/ml respectively. At intermediate doses growth and melanization were found to show a pattern of change over between growth and melanization and finally reached at an inverse relation at the respective optimal dose of response. Compared with defined sphingolipids, C2 ceramide and sphingosine-1-phosphate, the results were mostly corroborative. The duality of biological response of sphingolipids as reported in numerous studies was comparable for the PTLF suggesting that its active component is a sphingolipid and showing its use for pigment recovery in vitiligo.

  12. Specific biodetection of B16 mouse melanoma in vivo by syngeneic monoclonal antibody

    International Nuclear Information System (INIS)

    The specific detection of tumors in vivo using a radiolabeled syngeneic monoclonal antibody made by fusion of P3U1 (BALB/c myeloma cells) and C57BL/6 spleen cells primed with syngeneic B16 melanoma cells was investigated by color imaging, autoradiography, and biodistribution. The radiolabeled antimelanoma antibody specifically accumulated only in the tumor lesions, whereas no radioactivity was observed in normal tissues or organs. The distribution patterns of the radioactive antibody in the tumor lesions depended on the sizes of the tumor. Almost the entire region of the small metastatic tumor in lymph nodes was labeled, whereas the radioactive antibody was irregularly localized mainly in the center of the medium-sized tumor. However, only the peripheral region of the large primary tumor was labeled. The highest uptake of radioactivity (tumor:blood ratio) was observed in the small lymph node metastatic tumor lesions rather than in the large primary tumor. Furthermore, high resolution color imaging of B16 melanoma was also obtained by using 125I-labeled monoclonal antibody. Tumor location was specifically visible without subtraction or enhancement methods 3-5 days after injection of the radiolabeled antibody

  13. [6]-Shogaol inhibits melanogenesis in B16 mouse melanoma cells through activation of the ERK pathway

    Institute of Scientific and Technical Information of China (English)

    Cheng YAO; Jang-hee OH; Inn Gyung OH; Chi-hyun PARK; Jin Ho CHUNG

    2013-01-01

    Aim: To investigate the effect of [6]-shogaol,an active ingredient in ginger,on melanogenesis and the underlying mechanisms.Methods: B16F10 mouse melanoma cells were tested.Cell viability was determined with the MTT assay.Melanin content and tyrosinase activity were analyzed with a spectrophotometer.The protein expression of tyrosinase and microphthalmia associated transcription factor (MITF),as well as phosphorylated or total ERK1/2 and Akt were measured using Western blot.Results: Treatment of the cells with [6]-shogaol (1,5,10 μmol/L) reduced the melanin content in a concentration-dependent manner.[6]-Shogaol (5 and 10 μmol/L) significantly decreased the intracellular tyrosinase activity,and markedly suppressed the expression levels of tyrosinase and MITF proteins in the cells.Furthermore,[6]-shogaol (10 μmol/L) activated ERK,which was known to negatively regulate melanin synthesis in these cells.Pretreatment with the specific ERK pathway inhibitor PD98059 (20 μmol/L) greatly attenuated the inhibition of melanin synthesis by [6]-shogaol (10 μmol/L).Conclusion: The results demonstrate that [6]-shogaol inhibits melanogenesis in B16F10 mouse melanoma cells via activating the ERK pathway.

  14. CCR4 is critically involved in effective antitumor immunity in mice bearing intradermal B16 melanoma.

    Science.gov (United States)

    Matsuo, Kazuhiko; Itoh, Tatsuki; Koyama, Atsushi; Imamura, Reira; Kawai, Shiori; Nishiwaki, Keiji; Oiso, Naoki; Kawada, Akira; Yoshie, Osamu; Nakayama, Takashi

    2016-08-01

    CCR4 is a major chemokine receptor expressed by Treg cells and Th17 cells. While Treg cells are known to suppress antitumor immunity, Th17 cells have recently been shown to enhance the induction of antitumor cytotoxic T lymphocytes. Here, CCR4-deficient mice displayed enhanced tumor growth upon intradermal inoculation of B16-F10 melanoma cells. In CCR4-deficient mice, while IFN-γ+CD8+ effector T cells were decreased in tumor sites, IFN-γ+CD8+ T cells and Th17 cells were decreased in regional lymph nodes. In wild-type mice, CD4+IL-17A+ cells, which were identified as CCR4+CD44+ memory Th17, were found to be clustered around dendritic cells expressing MDC/CCL22, a ligand for CCR4, in regional lymph nodes. Compound 22, a CCR4 antagonist, also enhanced tumor growth and decreased Th17 cells in regional lymph nodes in tumor-bearing mice treated with Dacarbazine. In contrast, CCR6 deficiency did not affect the tumor growth and the numbers of Th17 cells in regional lymph nodes. These findings indicate that CCR4 is critically involved in regional lymph node DC-Th17 cell interactions that are necessary for Th17 cell-mediated induction of antitumor CD8+ effector T cells in mice bearing B16 melanoma. PMID:27132989

  15. The killing effect of 4-S-cysteaminylphenol, a newly synthesised melanin precursor, on B16 melanoma cell lines.

    OpenAIRE

    Yamada, I.; Seki, S.; Ito, S.; Suzuki, S.; Matsubara, O.; Kasuga, T.

    1991-01-01

    We have examined the killing effect of 4-S-cysteaminylphenol (4-S-CAP), a newly synthesised melanin precursor, on B16 melanoma cell lines possessing different melanin-producing activities and found it to be particularly effective in heavily melanised melanoma cells, but less so in moderately melanised melanoma cells, and having no effect on amelanotic melanoma cells and nonmelanoma cells. Thus, it was found that the killing effect of 4-S-CAP is highly dependent upon the synthesis of melanin a...

  16. Quantification of B16 Melanoma Cells in Lungs Using Triplex Q-PCR - A New Approach to Evaluate Melanoma Cell Metastasis and Tumor Control

    DEFF Research Database (Denmark)

    Sorensen, Maria R; Pedersen, Sara R; Lindkvist, Annika; Christensen, Jan P; Thomsen, Allan Randrup

    2014-01-01

    survival once the tumor has metastasized. In the present study, we have developed a new assay for quantitative analysis of B16 melanoma metastasis in the lungs. We have used a triplex Q-PCR to determine the expression of the melanoma genes GP100/Pmel and tyrosinase-related protein 2 (TRP-2), and found that...

  17. Mechanism of low dose X-radiation influencing B16 melanoma blood-borne pulmonary metastases

    International Nuclear Information System (INIS)

    After whole body exposed to 7.5 cGy X-ray, the C57BL/6 mice were I. V. injected with 125IUdR labelled B16 melanoma cells, the proportion of surviving labelled cells retained in lungs was detected at 24 hours after injection, and found that the surviving cells in the lungs of irradiated mice were significantly decreased. Meanwhile, the immunofunctions were tested at 24 hours after irradiation, the results showed that the number of nucleate cells and NK cytotoxity in spleens, and the phagocytotic function of macrophages in vivo were increased obviously for the irradiated mice. The results suggested that the enhancement of NK cytotoxity and macrophage phagocytotic function might be one of the important reasons for low dose radiation accelerating the clearance of tumor cells from the lungs

  18. Atmospheric-pressure plasma jet characterization and applications on melanoma cancer treatment (B/16-F10)

    Energy Technology Data Exchange (ETDEWEB)

    Mashayekh, Shahriar [Physics Department, Shahid Beheshti University, G.C., Evin, 19839-63113 Tehran, Islamic Republic of Iran (Iran, Islamic Republic of); Rajaee, Hajar; Hassan, Zuhir M. [Imonology Department, Faculty of Medical Science, Tarbiat Modarres University, Tehran (Iran, Islamic Republic of); Akhlaghi, Morteza [Laser-Plasma Research Institute, Shahid Beheshti University, G.C., Evin, 19839-63113 Tehran, Islamic Republic of Iran (Iran, Islamic Republic of); Shokri, Babak [Physics Department and Laser-Plasma Research Institute, Shahid Beheshti University, G.C., Evin, 19839-63113 Tehran, Islamic Republic of Iran (Iran, Islamic Republic of)

    2015-09-15

    A new approach in medicine is the use of cold plasma for various applications such as sterilization blood coagulation and cancer cell treatment. In this paper, a pin-to-hole plasma jet for biological applications has been designed and manufactured and characterized. The characterization includes power consumption via Lissajous method, thermal behavior of atmospheric-pressure plasma jet by using Infra-red camera as a novel method and using Speicair software to determine vibrational and transitional temperatures, and optical emission spectroscopy to determine the generated species. Treatment of Melanoma cancer cells (B16/F10) was also implemented, and tetrazolium salt dye (MTT assay) and flow cytometry were used to evaluate viability. Effect of ultraviolet photons on cancerous cells was also observed using an MgF{sub 2} crystal with MTT assay. Finally, in-vivo studies on C57 type mice were also done in order to have a better understanding of the effects in real conditions.

  19. Atmospheric-pressure plasma jet characterization and applications on melanoma cancer treatment (B/16-F10)

    Science.gov (United States)

    Mashayekh, Shahriar; Rajaee, Hajar; Akhlaghi, Morteza; Shokri, Babak; Hassan, Zuhir M.

    2015-09-01

    A new approach in medicine is the use of cold plasma for various applications such as sterilization blood coagulation and cancer cell treatment. In this paper, a pin-to-hole plasma jet for biological applications has been designed and manufactured and characterized. The characterization includes power consumption via Lissajous method, thermal behavior of atmospheric-pressure plasma jet by using Infra-red camera as a novel method and using Speicair software to determine vibrational and transitional temperatures, and optical emission spectroscopy to determine the generated species. Treatment of Melanoma cancer cells (B16/F10) was also implemented, and tetrazolium salt dye (MTT assay) and flow cytometry were used to evaluate viability. Effect of ultraviolet photons on cancerous cells was also observed using an MgF2 crystal with MTT assay. Finally, in-vivo studies on C57 type mice were also done in order to have a better understanding of the effects in real conditions.

  20. Atmospheric-pressure plasma jet characterization and applications on melanoma cancer treatment (B/16-F10)

    International Nuclear Information System (INIS)

    A new approach in medicine is the use of cold plasma for various applications such as sterilization blood coagulation and cancer cell treatment. In this paper, a pin-to-hole plasma jet for biological applications has been designed and manufactured and characterized. The characterization includes power consumption via Lissajous method, thermal behavior of atmospheric-pressure plasma jet by using Infra-red camera as a novel method and using Speicair software to determine vibrational and transitional temperatures, and optical emission spectroscopy to determine the generated species. Treatment of Melanoma cancer cells (B16/F10) was also implemented, and tetrazolium salt dye (MTT assay) and flow cytometry were used to evaluate viability. Effect of ultraviolet photons on cancerous cells was also observed using an MgF2 crystal with MTT assay. Finally, in-vivo studies on C57 type mice were also done in order to have a better understanding of the effects in real conditions

  1. Effects of Quercetin on Mushroom Tyrosinase and B16-F10 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Ken-ichi Nihei

    2007-05-01

    Full Text Available In searching for tyrosinase inhibitors from plants using L-3,4-dihydroxyphenylalanine (L-DOPA as a substrate, quercetin was found to be partially oxidized to the corresponding o-quinone under catalysis by mushroom tyrosinase (EC 1.14.18.1. Simultaneously, L-DOPA was also oxidized to dopaquinone and both o-quinones were further oxidized, respectively. The remaining quercetin partially formed adducts with dopaquinone through a Michael type addition. In general, flavonols form adducts with dopaquinone as long as their 3-hydroxyl group is free. Quercetin enhanced melanin production per cell in cultured murine B16-F10 melanoma cells, but this effect may be due in part to melanocytotoxicity. The concentration leading to 50% viable cells lost was established as 20 μM and almost complete lethality was observed at 80 μM.

  2. Evaluation of Depigmenting Activity by 8-Hydroxydaidzein in Mouse B16 Melanoma Cells and Human Volunteers

    Directory of Open Access Journals (Sweden)

    Ching-Gong Lin

    2009-09-01

    Full Text Available In our previous study, 8-hydroxydaidzein (8-OHDe was demonstrated to be a potent and unique suicide substrate of mushroom tyrosinase. In this study, the compound was evaluated for in vitro cellular tyrosinase and melanogenesis inhibitory activities in mouse B16 melanoma cells and for in vivo skin-whitening activity in human volunteers. Tyrosinase activity and melanogenesis in the cell culture incubated with 10 µM of 8-OHDe were decreased to 20.1% and 51.8% of control, respectively, while no obvious cytotoxicity was observed in this concentration. In contrast, a standard tyrosinase inhibitor, kojic acid, showed 69.9% and 71.3% of control in cellular tyrosinase and melanogenesis activity, respectively, at a concentration as high as 100 µM. Hence, 8-OHDe exhibited more than an inhibitory effects on melanin production in B16 cells 10-fold stronger than kojic acid. In addition, when a cream containing 4% 8-OHDe was applied to human skin in an in vivo study, significant increases in the dL*-values were observed after three weeks. Moreover, the increase in the dL*-values after 8-week treatment with 4% 8-OHDe (from -0.57 to 1.94 is stronger than those of 2% 8-OHDe treatment (from 0.26 to 0.94 and 2% ascorbic acid-2-glucoside treatment (from 0.07 to 1.54. From the results of the study, it was concluded that 8-OHDe, the potent suicide substrate of mushroom tyrosinase, has depigmenting activities in both mouse melanoma cells and in human volunteers. Thus, the compound has significant potential for use in cosmetics as a skin-whitening ingredient.

  3. Evaluation of depigmenting activity by 8-hydroxydaidzein in mouse B16 melanoma cells and human volunteers.

    Science.gov (United States)

    Tai, Sorgan Shou-Ku; Lin, Ching-Gong; Wu, Mon-Han; Chang, Te-Sheng

    2009-10-01

    In our previous study, 8-hydroxydaidzein (8-OHDe) was demonstrated to be a potent and unique suicide substrate of mushroom tyrosinase. In this study, the compound was evaluated for in vitro cellular tyrosinase and melanogenesis inhibitory activities in mouse B16 melanoma cells and for in vivo skin-whitening activity in human volunteers. Tyrosinase activity and melanogenesis in the cell culture incubated with 10 microM of 8-OHDe were decreased to 20.1% and 51.8% of control, respectively, while no obvious cytotoxicity was observed in this concentration. In contrast, a standard tyrosinase inhibitor, kojic acid, showed 69.9% and 71.3% of control in cellular tyrosinase and melanogenesis activity, respectively, at a concentration as high as 100 microM. Hence, 8-OHDe exhibited more than an inhibitory effects on melanin production in B16 cells 10-fold stronger than kojic acid. In addition, when a cream containing 4% 8-OHDe was applied to human skin in an in vivo study, significant increases in the dL*-values were observed after three weeks. Moreover, the increase in the dL*-values after 8-week treatment with 4% 8-OHDe (from -0.57 to 1.94) is stronger than those of 2% 8-OHDe treatment (from 0.26 to 0.94) and 2% ascorbic acid-2-glucoside treatment (from 0.07 to 1.54). From the results of the study, it was concluded that 8-OHDe, the potent suicide substrate of mushroom tyrosinase, has depigmenting activities in both mouse melanoma cells and in human volunteers. Thus, the compound has significant potential for use in cosmetics as a skin-whitening ingredient. PMID:20057943

  4. B16F1 melanoma cells upregulate melanin synthesis after photodynamic therapy

    International Nuclear Information System (INIS)

    Full text: The success of photodynamic therapy (PDT) of melanotic tumors is severely limited by insufficient penetration of light into deeper tissue layers. In this study, we analyzed the effect of PDT on the melanin production of the melanoma cell line B16F1. In vitro, these cells produce only little melanin. However, after PDT we found a dramatic elevation in intracellular melanin. Melanin production increased with, both, the concentration of the sensitizing agent and the light dose, and was found to continue for several hours after cell death. PDT-induced melanin synthesis was not prevented by the addition of cycloheximide or actinomycin D prior to irradiation, indicating that de-novo protein synthesis and transcriptional activity are not required for this effect. We also analyzed tyrosinase activity, a key enzyme in melanin biosynthesis, in PDT-treated B16 cells. Tyrosinase activity was found in PDT-treated as well as untreated cells. Cell fractionation experiments showed that tyrosinase was present in the cytosolic as well as the melanosomal fractions of, both, PDT-treated (melanin-high) as well as untreated (melanin-low) cells. These data indicate that PDT-induced production of melanin is not controlled at the transcriptional or translational level and that tyrosinase is not likely an essential regulator in this process. (author)

  5. Cytosolic DNA Sensor Upregulation Accompanies DNA Electrotransfer in B16.F10 Melanoma Cells.

    Science.gov (United States)

    Znidar, Katarina; Bosnjak, Masa; Cemazar, Maja; Heller, Loree C

    2016-01-01

    In several preclinical tumor models, antitumor effects occur after intratumoral electroporation, also known as electrotransfer, of plasmid DNA devoid of a therapeutic gene. In mouse melanomas, these effects are preceded by significant elevation of several proinflammatory cytokines. These observations implicate the binding and activation of intracellular DNA-specific pattern recognition receptors or DNA sensors in response to DNA electrotransfer. In tumors, IFNβ mRNA and protein levels significantly increased. The mRNAs of several DNA sensors were detected, and DAI, DDX60, and p204 tended to be upregulated. These effects were accompanied with reduced tumor growth and increased tumor necrosis. In B16.F10 cells in culture, IFNβ mRNA and protein levels were significantly upregulated. The mRNAs for several DNA sensors were present in these cells; DNA-dependent activator of interferon regulatory factor (DAI), DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 (DDX60), and p204 were significantly upregulated while DDX60 protein levels were coordinately upregulated. Upregulation of DNA sensors in tumors could be masked by the lower transfection efficiency compared to in vitro or to dilution by other tumor cell types. Mirroring the observation of tumor necrosis, cells underwent a significant DNA concentration-dependent decrease in proliferation and survival. Taken together, these results indicate that DNA electrotransfer may cause the upregulation of several intracellular DNA sensors in B16.F10 cells, inducing effects in vitro and potentially in vivo. PMID:27271988

  6. Comparison of the inhibitory effects of vitamin E analogues on melanogenesis in mouse B16 melanoma cells

    OpenAIRE

    Kamei, Yuto; Otsuka, Yuri; Abe, Kouichi

    2009-01-01

    The effect of eight vitamin E analogues (d-α-, dl-α-, d-β-, d-γ-, and d-δ-tocopherols, d-α- and dl-α-tocopheryl acetates) and 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMC) on melanogenesis were compared in mouse B16 melanoma cells. D-β-tocopherol at 250 μg ml−1 inhibited not only 28% of melanin synthesis in B16 cells, but also 34% of the tyrosinase activity, a very important cascade enzyme involved in the synthesis of melanin in melanoma cells. D-γ-tocopherol also strongly inhibited up to 39% ...

  7. Electroporation transiently decreases GJB2 (connexin 26) expression in B16/BL6 melanoma cell line.

    Science.gov (United States)

    Rangel, Marcelo Monte Mór; Chaible, Lucas Martins; Nagamine, Marcia Kazumi; Mennecier, Gregory; Cogliati, Bruno; de Oliveira, Krishna Duro; Fukumasu, Heidge; Sinhorini, Idércio Luiz; Mir, Lluis Maria; Dagli, Maria Lúcia Zaidan

    2015-02-01

    Connexins are proteins that form gap junctions. Perturbations in the cell membrane reportedly promote changes in the expression profile of connexins. Electroporation promotes destabilization by applying electrical pulses, and this procedure is used in electrochemotherapy and gene therapy, among others. This in vitro work aimed to study the interference of electroporation on the expression profile of GJB2 (Cx26 gene) and Connexin 26 in melanoma cell line B16/BL6. The techniques of immunocytochemistry, Western blot, and real-time PCR were used. After electroporation, cells showed a transient decrease in GJB2 mRNA. The immunostaining of Cx26 showed no noticeable change after electroporation at different time points. However, Western blot showed a significant reduction in Cx26 30 min after electroporation. Our results showed that electroporation interferes transiently in the expression of Connexin 26 in melanoma and are consistent with the idea that electroporation is a process of intense stress that promotes cell homeostatic imbalance and results in disruption of cell physiological processes such as transcription and translation. PMID:25298064

  8. An ester extract of Cochinchina momordica seeds induces differentiation of melanoma B16 F1 cells via MAPKs signaling.

    Science.gov (United States)

    Zhao, Lian-Mei; Han, Li-Na; Ren, Feng-Zhi; Chen, Shu-Hong; Liu, Li-Hua; Wang, Ming-Xia; Sang, Mei-Xiang; Shan, Bao-En

    2012-01-01

    Cochinchina momordica seeds (CMS) have been widely used due to antitumor activity by Mongolian tribes of China. However, the details of the underlying mechanisms remain unknown. In the present study, we found that an EtOAc (ethyl ester) extract of CMS (CMSEE) induced differentiation and caused growth inhibition of melanoma B16 F1 cells. CMSEE at the concentration of 5-200 μg/ml exhibited strongest anti-proliferative effects on B16 F1 cells among other CMS fractions (water or petroleum ether). Moreover, CMSEE induced melanoma B16 F1 cell differentiation, characterized by dendrite-like outgrowth, increasing melanogenesis production, as well as enhancing tyrosinase activity. Western blot analysis showed that sustained phosphorylation of p38 MAP accompanied by decrease in ERK1/2 and JNK dephosphorylation were involved in CMSEE-induced B16 F1 cell differentiation. Notably, 6 compounds that were isolated and identified may be responsible for inducing differentiation of CMSEE. These results indicated that CMSEE contributes to the differentiation of B16 F1 cells through modulating MAPKs activity, which may throw some light on the development of potentially therapeutic strategies for melanoma treatment. PMID:23098473

  9. Nutritional lipid supply can control the heat shock response of B16 melanoma cells in culture.

    Science.gov (United States)

    Péter, Mária; Balogh, Gábor; Gombos, Imre; Liebisch, Gerhard; Horváth, Ibolya; Török, Zsolt; Nagy, Enikő; Maslyanko, Andriy; Benkő, Sándor; Schmitz, Gerd; Harwood, John L; Vígh, László

    2012-11-01

    The in vitro culture of cells offers an extremely valuable method for probing biochemical questions and many commonly-used protocols are available. For mammalian cells a source of lipid is usually provided in the serum component. In this study we examined the question as to whether the nature of the lipid could become limiting at high cell densities and, therefore, prospectively influence the metabolism and physiology of the cells themselves. When B16 mouse melanoma cells were cultured, we noted a marked decrease in the proportions of n-3 and n-6 polyunsaturated fatty acids (PUFAs) with increasing cell density. This was despite considerable quantities of these PUFAs still remaining in the culture medium and seemed to reflect the preferential uptake of unesterified PUFA rather than other lipid classes from the media. The reduction in B16 total PUFA was reflected in changes in about 70% of the molecular species of membrane phosphoglycerides which were analysed by mass spectrometry. The importance of this finding lies in the need for n-3 and n-6 PUFA in mammalian cells (which cannot synthesize their own). Although the cholesterol content of cells was unchanged the amount of cholesterol enrichment in membrane rafts (as assessed by fluorescence) was severely decreased, simultaneous with a reduced heat shock response following exposure to 42°C. These data emphasize the pivotal role of nutrient supply (in this case for PUFAs) in modifying responses to stress and highlight the need for the careful control of culture conditions when assessing cellular responses in vitro. PMID:22583025

  10. Cutaneous melanoma in solid organ transplant patients.

    Science.gov (United States)

    Russo, I; Piaserico, S; Belloni-Fortina, A; Alaibac, M

    2014-08-01

    Solid organ transplant patients are at greatly increased risk of developing a wide variety of skin cancers, particularly epithelial skin cancers. On the other hand, it is well known that an intact immune system limits the development of benign melanocytic lesions. The eruptive nevi phenomenon, which we can observe in solid organ transplant recipients, is indicative of the relationship between melanocyte proliferation and immune system. Regression of melanocytic nevi after restoration of complete immune responsiveness is a further clinical example the role of immunosurveillance on melanocyte proliferation. However, melanoma incidence in organ transplant recipients appears only 2-3 folds higher than in general population. To this regard, organ transplant recipients who develop de novo melanomas thicker than 2mm seem to have a significantly worse outcome with a greatly increased risk of dying of metastatic melanoma, whereas those who develop a ≤2 mm thickness melanoma seem to have a prognosis similar to that of the general population. Furthermore, there is no evidence supporting an increased risk of melanoma recurrences after transplant in patients with a history of low-risk melanoma. Melanoma is also one of the most frequent and lethal donor-derived malignancies suggesting that a history of invasive melanoma should be considered an absolute contraindication to donation. The aim of this review is to investigate the relationship between immunosuppression and melanoma and to discuss its clinical implications for the management of transplant-associated melanoma. PMID:25068225

  11. Anti-Melanogenic Property of Geoditin A in Murine B16 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Chun-Tao Che

    2012-02-01

    Full Text Available Geoditin A, an isomalabaricane triterpene isolated from marine sponge Geodia japonica, has been demonstrated to induce apoptosis in leukemia HL60 cells and human colon HT29 cancer cells through an oxidative stress, a process also interfering with normal melanogenesis in pigment cells. Treatment of murine melanoma B16 cells with geoditin A decreased expression of melanogenic proteins and cell melanogenesis which was aggravated with adenylate cyclase inhibitor SQ22536, indicating melanogenic inhibition was mediated through a cAMP-dependent signaling pathway. Immunofluorescence microscopy and glycosylation studies revealed abnormal glycosylation patterns of melanogenic proteins (tyrosinase and tyrosinase-related protein 1, and a co-localization of tyrosinase with calnexin (CNX and lysosome-associated membrane protein 1 (LAMP-1, implicating a post-translational modification in the ER and a degradation of tyrosinase in the lysosome. Taken together, potent anti-melanogenic property and the relatively low cytotoxicity of geoditin A have demonstrated its therapeutic potential as a skin lightening agent.

  12. Melanoma-targeted delivery system (part 2): Synthesis, radioiodination and biological evaluation in B16F0 bearing mice.

    Science.gov (United States)

    El Aissi, Radhia; Miladi, Imen; Chezal, Jean-Michel; Chavignon, Olivier; Miot-Noirault, Elisabeth; Moreau, Emmanuel

    2016-09-14

    Here we report the synthesis and radiolabelling with iodine-125 of a melanoma-selective prodrug (17a*) and its parent drug IUdR. The in vivo and ex vivo biodistributions of [(125)I](17a*) and [(125)I]IUdR were evaluated in a model of melanoma B16F0-bearing mice. The pharmacokinetic profile of [(125)I](17a*) suggests rapid release of the active drug [(125)I]IUdR after i.v. administration of [(125)I](17a*). Preliminary metabolism studies in dedicated compartments (i.e. blood, urine and tumour) yielded results consistent with this hypothesis. PMID:27214141

  13. Mechanism of low-level ionizing radiation in inhibiting B16 melanoma blood-borne pulmonary metastasis

    International Nuclear Information System (INIS)

    Objective: To study the mechanism of low-level ionizing radiation in inhibiting B16 melanoma blood-borne pulmonary metastasis. Method: 125I-labelled B16 melanoma cells were used to investigate the effect of low dose X-irradiation on the distribution and clearance of tumor cells in mice. Results: After whole body 7.5 cGy x-irradiation, the clearance of tumor cells was significantly increased from lungs of mice. The residual numbers of tumor cells were markedly lower than those of control in blood, spleen, liver and lungs (P<0.05-0.01). The cytotoxicity of murine splenic NK cells, LTR and the phagocytosis of macrophages augmented significantly after the mice were irradiated with low dose X-rays. Conclusion: These results suggest that the enhancement of NK cytotoxicity and macrophage phagocytotic function might be one of the important reasons why low dose radiation can accelerate the clearance of tumor cells from the lungs

  14. Immune-mediated regression of established B16F10 melanoma by intratumoral injection of attenuated Toxoplasma gondii protects against rechallenge.

    Science.gov (United States)

    Baird, Jason R; Byrne, Katelyn T; Lizotte, Patrick H; Toraya-Brown, Seiko; Scarlett, Uciane K; Alexander, Matthew P; Sheen, Mee Rie; Fox, Barbara A; Bzik, David J; Bosenberg, Marcus; Mullins, David W; Turk, Mary Jo; Fiering, Steven

    2013-01-01

    Immune recognition of tumors can limit cancer development, but antitumor immune responses are often blocked by tumor-mediated immunosuppression. Because microbes or microbial constituents are powerful adjuvants to stimulate immune responses, we evaluated whether intratumoral administration of a highly immunogenic but attenuated parasite could induce rejection of an established poorly immunogenic tumor. We treated intradermal B16F10 murine melanoma by intratumoral injection of an attenuated strain of Toxoplasma gondii (cps) that cannot replicate in vivo and therefore is not infective. The cps treatment stimulated a strong CD8(+) T cell-mediated antitumor immune response in vivo that regressed established primary melanoma. The cps monotherapy rapidly modified the tumor microenvironment, halting tumor growth, and subsequently, as tumor-reactive T cells expanded, the tumors disappeared and rarely returned. The treatment required live cps that could invade cells and also required CD8(+) T cells and NK cells, but did not require CD4(+) T cells. Furthermore, we demonstrate that IL-12, IFN-γ, and the CXCR3-stimulating cytokines are required for full treatment efficacy. The treatment developed systemic antitumor immune activity as well as antitumor immune memory and therefore might have an impact against human metastatic disease. The approach is not specific for either B16F10 or melanoma. Direct intratumoral injection of cps has efficacy against an inducible genetic melanoma model and transplantable lung and ovarian tumors, demonstrating potential for broad clinical use. The combination of efficacy, systemic antitumor immune response, and complete attenuation with no observed host toxicity demonstrates the potential value of this novel cancer therapy. PMID:23225891

  15. Melanin biosynthesis inhibitory activity of a compound isolated from young green barley (Hordeum vulgare L.) in B16 melanoma cells.

    Science.gov (United States)

    Meng, Tian Xiao; Irino, Nobuto; Kondo, Ryuichiro

    2015-07-01

    In the course to find compounds that inhibit melanin biosynthesis (i.e., whitening agents), we evaluated the effects of the methanol-soluble fraction (i.e., the water-soluble portion of methanol extracts-CHP20P-MeOH eluted fraction) from young green barley leaves on melanin production in B16 melanoma cells. Activity-guided fractionation led to an isolate called tricin (compound 1) as an inhibitory compound of melanin production in B16 melanoma cells. Furthermore, tricin analogs such as tricetin, tricetin trimethyl ether, luteolin, and apigenin were used for analyzing the structure-activity relationships (SAR) of 5,7-dihydroxyflavones studies. Tricin demonstrated stronger inhibitory activity compared to three other compounds. The results suggest that a hydroxyl group at the C-4' position and methoxy groups at the C-3',5' positions of the tricin skeleton may have important roles in this inhibitory activity in B16 melanoma cells. Our results suggest that tricin inhibits melanin biosynthesis with higher efficacy than arbutin, and it could be used as a whitening agent. PMID:25827948

  16. Cyclohexanediol bis-ethylhexanoate inhibits melanogenesis of murine B16 melanoma and UV-induced pigmentation in human skin.

    Science.gov (United States)

    Lim, Joo Hyuck; Park, So-Hyun; Kim, Myoung Rae; Yoo, Byoung-Sam; Yang, Jae Chan; Cheong, In Woo; Kim, Jung Hyun; Cho, Jin Hun

    2013-01-01

    The role of cyclohexane diester analogues in the formation of melanin has been recently reported. In the present study, we investigated the inhibitory effect of cyclohexanediol bis-ethylhexanoate (CHEH) on melanogenesis in B16 melanoma cells and on UV-B-induced pigmentation in human skin. CHEH significantly reduced the melanin content in a dose-dependent manner, without cytotoxic effects at the effective concentrations. Moreover, CHEH dose-dependently inhibited tyrosinase activity in B16 melanoma cells, as confirmed by Western blot analysis of the tyrosinase protein levels. However, tyrosinase transcript levels remained unchanged under the same experimental conditions. These results indicate that CHEH inhibited melanogenesis in B16 melanoma cells by regulating tyrosinase activity at the post-transcriptional level. On the other hand, in a cell-free system, CHEH did not inhibit tyrosinase activity. This indicated that CHEH suppressed the pigmentation of melanocytes by indirectly regulating tyrosinase activity. Finally, in a clinical trial, a cream containing 1.0% CHEH showed good whitening effect on UV-induced pigmented human skin without adverse effects. In conclusion, we suggest that CHEH may be an effective inhibitor of melanogenesis and useful effects in the treatment of hyperpigmented disorders. PMID:23258078

  17. Inhibition of cell proliferation, migration and invasion of B16-F10 melanoma cells by α-mangostin

    Energy Technology Data Exchange (ETDEWEB)

    Beninati, Simone, E-mail: beninati@bio.uniroma2.it [Department of Biology, University “Tor Vergata”, Rome (Italy); Oliverio, Serafina [Department of Biology, University “Tor Vergata”, Rome (Italy); Cordella, Martina [Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome (Italy); Rossi, Stefania; Senatore, Cinzia [Regina Elena National Cancer Institute, Rome (Italy); Liguori, Immacolata; Lentini, Alessandro; Piredda, Lucia [Department of Biology, University “Tor Vergata”, Rome (Italy); Tabolacci, Claudio [Department of Biology, University “Tor Vergata”, Rome (Italy); Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome (Italy)

    2014-08-08

    Highlights: • We studied the anticancer potential of a new emerging molecule, α-mangostin (α-M). • We provide first evidences on the effects of α-M on transglutaminase activity. • We deeply examined the antimetastatic effects of α-M through many in vitro assays. • Proteomic analysis revealed that α-M promotes a reorganization at cellular level. - Abstract: In this study, we have evaluated the potential antineoplastic effects of α-mangostin (α-M), the most representative xanthone in Garcinia mangostana pericarp, on melanoma cell lines. This xanthone markedly inhibits the proliferation of high-metastatic B16-F10 melanoma cells. Furthermore, by deeply analyzing which steps in the metastatic process are influenced by xanthone it was observed that α-M strongly interferes with homotypic aggregation, adhesion, plasticity and invasion ability of B16-F10 cells, probably by the observed reduction of metalloproteinase-9 activity. The antiproliferative and antimetastatic properties of α-M have been established in human SK-MEL-28 and A375 melanoma cells. In order to identify pathways potentially involved in the antineoplastic properties of α-M, a comparative mass spectrometry proteomic approach was employed. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of α-M on melanoma.

  18. Inhibition of cell proliferation, migration and invasion of B16-F10 melanoma cells by α-mangostin

    International Nuclear Information System (INIS)

    Highlights: • We studied the anticancer potential of a new emerging molecule, α-mangostin (α-M). • We provide first evidences on the effects of α-M on transglutaminase activity. • We deeply examined the antimetastatic effects of α-M through many in vitro assays. • Proteomic analysis revealed that α-M promotes a reorganization at cellular level. - Abstract: In this study, we have evaluated the potential antineoplastic effects of α-mangostin (α-M), the most representative xanthone in Garcinia mangostana pericarp, on melanoma cell lines. This xanthone markedly inhibits the proliferation of high-metastatic B16-F10 melanoma cells. Furthermore, by deeply analyzing which steps in the metastatic process are influenced by xanthone it was observed that α-M strongly interferes with homotypic aggregation, adhesion, plasticity and invasion ability of B16-F10 cells, probably by the observed reduction of metalloproteinase-9 activity. The antiproliferative and antimetastatic properties of α-M have been established in human SK-MEL-28 and A375 melanoma cells. In order to identify pathways potentially involved in the antineoplastic properties of α-M, a comparative mass spectrometry proteomic approach was employed. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of α-M on melanoma

  19. Synthesis, in vitro binding and biodistribution in B16 melanoma-bearing mice of new iodine-125 spermidine benzamide derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Moreau, Marie-France [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France); Papon, Janine [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France); Labarre, Pierre [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France); Moins, Nicole [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France)]. E-mail: moins@inserm484.u-clermont1.fr; Borel, Michele [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France); Bayle, Martine [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France); Bouchon, Bernadette [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France); Madelmont, Jean-Claude [INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex (France); Univ d' Auvergne, F-63000 Clermont-Ferrand (France); Centre Jean Perrin, F-63000 Clermont-Ferrand (France)

    2005-05-01

    In the course of our investigations aimed at improving the biological characteristics of iodobenzamides for melanoma therapeutic applications, four new derivatives containing a spermidine chain have been prepared and radiolabeled with {sup 125}I. In vitro studies showed that all compounds displayed high affinity for melanin superior to the reference compound BZA, thus validating our experimental approach. In vivo biodistribution was investigated in B16 melanoma-bearing mice. All four compounds, particularly benzamide 3, showed accumulation in the tumor, but lower, however, than that of BZA. Moreover, high concentrations of radioactivity in other organs, namely, the liver and lung, demonstrated nonspecific tumoral uptake. In view of these results, compounds 1 2 3 4 do not appear to be suitable radiopharmaceuticals for melanoma radionuclide therapy.

  20. Studies on the mechanisms responsible for inhibition of experimental metastasis of B16-F10 murine melanoma by pentoxifylline.

    Science.gov (United States)

    Gude, R P; Binda, M M; Presas, H L; Klein-Szanto, A J; Bonfil, R D

    1999-01-01

    Pentoxifylline (PTX), a methylxanthine derivative widely used as a hemorheological agent in the treatment of peripheral vascular disease, was studied to unveil the mechanisms responsible for its inhibitory action on B16-F10 experimental metastasis. In vitro pretreatment of B16-F10 cells with noncytotoxic concentrations of PTX significantly inhibited their adhesion to reconstituted basement membrane Matrigel(R) and type IV collagen as well as the relative activity of secreted 92 kD metalloproteinase. However, PTX pretreatment of B16-F10 cells did not affect their in vitro invasiveness. Heterotypic organ adhesion assays carried out with B16-F10 cells and suspended organ tissues demonstrated that pretreatment with noncytotoxic concentrations of PTX of both, tumor cells or lung tissue, brought about a dose-dependent inhibition of melanoma cell adhesion to lung. Immunohistochemical studies using antibodies against CD31 adhesion molecule (PECAM-1) revealed that B16-F10 cells adhere to lung endothelial cells. Our results suggest that PTX may exert its inhibitory effect on tumor lodgment, and as a consequence of that on experimental metastases, through an inhibitory action on cell adhesion molecules. PMID:10087444

  1. Evaluation of antioxidant and anti-melanogenic activities of different extracts from aerial parts of Nepeta binaludensis Jamzad in murine melanoma B16F10 cells

    Directory of Open Access Journals (Sweden)

    Zahra Tayarani-Najaran

    2016-06-01

    Conclusion: Taken together the data indicate that N. binaludensis has inhibitory activity on melanin synthesis with no cytotoxic effects in B16 melanoma cells. Therefore, it merits future investigations to apply as whitening agent in hyperpigmentation.

  2. LPA is a chemorepellent for B16 melanoma cells: action through the cAMP-elevating LPA5 receptor.

    Directory of Open Access Journals (Sweden)

    Maikel Jongsma

    Full Text Available Lysophosphatidic acid (LPA, a lipid mediator enriched in serum, stimulates cell migration, proliferation and other functions in many cell types. LPA acts on six known G protein-coupled receptors, termed LPA(1-6, showing both overlapping and distinct signaling properties. Here we show that, unexpectedly, LPA and serum almost completely inhibit the transwell migration of B16 melanoma cells, with alkyl-LPA(18:1 being 10-fold more potent than acyl-LPA(18:1. The anti-migratory response to LPA is highly polarized and dependent on protein kinase A (PKA but not Rho kinase activity; it is associated with a rapid increase in intracellular cAMP levels and PIP3 depletion from the plasma membrane. B16 cells express LPA(2, LPA(5 and LPA(6 receptors. We show that LPA-induced chemorepulsion is mediated specifically by the alkyl-LPA-preferring LPA(5 receptor (GPR92, which raises intracellular cAMP via a noncanonical pathway. Our results define LPA(5 as an anti-migratory receptor and they implicate the cAMP-PKA pathway, along with reduced PIP3 signaling, as an effector of chemorepulsion in B16 melanoma cells.

  3. Phenothiazinium dyes in association with diode red laser against B16F10 melanoma cells: in vitro study

    Science.gov (United States)

    Miranda, Anderson F.; Santos, Gustavo M. P.; de Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Sampaio, Fernando J. P.; Gomes Júnior, Rafael Araújo; Brugnera, Aldo; Gesteira, Maria F. M.; Zanin, Fátima A. A.; Pinheiro, Antônio Luiz B.; Vannier-Santos, Marcos A.

    2014-02-01

    In Brazil solar incidence is high and continuous throughout the year. Body exposure to sunlight may be a key point in the rates of individuals affected by melanoma and other types of skin cancer in many countries. Brazil already occupies the 15th place in the ranking of melanoma cases and the limitations presented by drugs used in the therapy of this cancer, new approaches are being used in an attempt to decrease the mortality of this malignancy. The aim of this study was to evaluate the effects of phenothiazinium dyes (PD) associated with laser light on murine melanoma (B16F10) in vitro by measuring cell growth using colorimetric assay before and after photodynamic therapy. We used a diode laser (λ660nm, 2.4 J/cm2, 40 mW, 60 s, CW) associated with PD at 12.5 μg/mL, time pre-irradiation of 30 minutes). The following groups were tested: control (LF-), PD (L-F+), Laser (L+F-), Laser + PD (L+F+). The results showed a significant reduction in cell growth in the group treated by the photodynamic therapy compared to the control at 24 and 48 h (p < 0.001). Were showing at 30 min PD has a dose-dependent response on B16F10 cells, but at 24 h did not demonstrated this response.

  4. Studies on glycoproteins produced by wild type and wheat germ agglutinin-resistant B16 mouse melanoma cells

    International Nuclear Information System (INIS)

    Two variants of B16 mouse melanoma cells have been selected in serum-free medium for their resistance to toxic levels of wheat germ agglutinin isolation 1 (WGA). Chromosome analysis and characteristic melanin production showed that the variants are derived from the parent mouse melanoma cell lines. However, the two variants were less tumorigenic in mice compared to the parent B16 mouse melanoma cells. The variants showed a marked decrease in cell agglutination with WGA. Cell agglutination with recin and peanut lectin was not different between the three cell lines, but the two variants showed a slight increase in agglutination with concanavalin A. The binding of 125I-labeled wheat germ agglutinin to the two variant cells was reduced compared to that of the parent cell. Glycoproteins secreted or shed by the three lines were isolated after growth in serum-free medium in the presence of [3He]glucosamine and bovine serum albumin (1%). These metabolically labeled products were fractionated on the basis of their interaction with WGA-Sepharose (2 mg/ml). The WGA-Sepharose affinity chromatographic data suggested a decrease in WGA-binding glycoprotein(s) secreted to the medium by the two variants. The WGA-bound glycoproteins from the two variants upon SDS-PAGE revealed three bands of approximate molecular weights, 92,000, 56,000, and 42,000, none of which were present in the parent cell line (50,000 molecular weight)

  5. Reduced paxillin expression contributes to the antimetastatic effect of 4-hydroxycoumarin on B16-F10 melanoma cells

    Directory of Open Access Journals (Sweden)

    Mandoki Juan J

    2008-05-01

    Full Text Available Abstract Background 4-Hydroxycoumarin (4-HC is a coumarin that lacks anticoagulant activity. 4-HC affects the cytoskeletal stability and decreases cell adhesion and motility of the melanoma cell line B16-F10. Together with integrins and other cytoskeletal proteins, paxillin participates in the regulation of cell adhesion and motility, acting as an adapter protein at focal adhesions. The present study determined the participation of paxillin in the reported effects of 4-HC and analyzed the role of paxillin in the formation of melanoma metastases. Results 4-HC decreased protein and mRNA levels of α- and β-paxillin isoforms in B16-F10 cells. Paxillin downregulation correlated with an inadequate translocation of paxillin to focal adhesions and a reduced phosphotyr118-paxillin pool. Consequently, 4-HC altered paxillin-mediated signaling, decreasing the phosphorylation of FAK and the level of GTP-bound Rac-1. These results partially explain the mechanism of the previously reported effects of 4-HC. Additionally, we studied the effect of 4-HC on metastatic potential of B16-F10 cells through experimental metastasis assays. In vitro treatment of cells with 4-HC inhibited their capability to originate pulmonary metastases. 4-HC did not affect cell proliferation or survival, demonstrating that its antimetastatic effect is unrelated to changes on cell viability. We also studied the importance of paxillin in metastasis by transfecting melanoma cells with paxillin-siRNA. Transfection produced a modest reduction on metastatic potential, indicating that: i paxillin plays a role as inducer of melanoma metastasis; and ii paxillin downregulation is not sufficient to explain the antimetastatic effect of 4-HC. Therefore, we evaluated other changes in gene expression by differential display RT-PCR analysis. Treatment with 4-HC produced a downregulation of Adhesion Regulating Molecule-1 (ARM-1, which correlated with a decreased adhesion of melanoma cells to lung

  6. Anti-cancer Effects of CME-1, a Novel Polysaccharide, Purified from the Mycelia of Cordyceps sinensis against B16-F10 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Thanasekaran Jayakumar

    2014-01-01

    Conclusions: These results indicate that CME-1 inhibited MMP-1 expressions in B16F10 melanoma cells through either NF-kB or ERK/p38 MAPK down regulation thereby inhibiting B16F10 cell migration. Therefore, we proposed that CME-1 might be developed as a therapeutic potential candidate for the treatment of cancer metastasis.

  7. Effect of Korean Red Sea Cucumber (Stichopus japonicus on Melanogenic Protein Expression in Murine B16 Melanoma

    Directory of Open Access Journals (Sweden)

    W.J. Yoon

    2010-01-01

    Full Text Available In this study, we therefore assessed the effects of S. japonicus on melanogenic protein expression of murine B16 melanoma cells. We obtained an S. japonicus extract by treatment with 80% EtOH and then successively partitioned it with n-hexane, CH2Cl2, EtOAc, BuOH and water. Present results indicated that the EtOAc fraction of the S. japonicus extract (SJE was effectively inhibited melanogenesis in murine B16 melanoma cells. We performed western blotting for melanogenic proteins to elucidate the mechanism of the effect of SJE on melanogenesis. SJE inhibited the expression of tyrosinase, Tyrosinase-Related Protein (TRP-1 and TRP-2. We also confirmed that SJE decreased the protein level of melanocyte-specific isoform of Microphthalmia-Associated Transcriptional Factor (MITF, leading decreased expression of tyrosinase and tyrosinase-related genes in the B16 melanoma cells. To test the applicability of SJE to the human skin, we used MTT assay to assess the cytotoxic effects of SJE on human keratinocyte HaCaT cells. The SJE exhibited low cytotoxicity at 20 μg mL-1. To test the applicability of S. japonicus as a cosmetic material with regard to its irritant or sensitization potential, we also performed human skin primary irritation tests, which showed no adverse reactions with S. japonicus usage. Hence, we suggest that S. japonicus be considered as a potential anti-melanogenic agent and may be effective for topical application for treating hyperpigmentation disorders.

  8. Suppressive Effect of Juzen-Taiho-To on Lung Metastasis of B16 Melanoma Cells In Vivo

    Directory of Open Access Journals (Sweden)

    Takako Matsuda

    2011-01-01

    Full Text Available Juzen-Taiho-To (JTT is well known to be one of Kampo (Japanese herbal medicine consisted of 10 component herbs and used for the supplemental therapy of cancer patients with remarkably success. However, the precise mechanisms by which JTT could favorably modify the clinical conditions of cancer patients are not well defined. The present study, therefore, was undertaken to examine the possible mechanisms of JTT on prevention of cancer metastasis using experimental mouse model. JTT was well mixed with rodent chow at concentrations of either 0.2 or 1.0%, and administered orally ad libitum, which was started 1 week before tumor cell injection and continue throughout the experiment. Oral administration of JTT at concentration 0.2 and 1.0% into C57BL/6 male mice significantly inhibited tumor metastasis in lungs, which was induced by the intravenous injection of 2 × 105 B16 melanoma cell. JTT at a concentration of 1.0% also significantly suppressed lung metastasis of B16 melanoma cell from hind footpad in C57BL/6 mice. In the second part of experiments, the influence of the depression of natural killer (NK cell, natural killer T (NKT cell and several types of cytokines on JTT-mediated inhibition of tumor cell metastasis. Intraperitoneal injection of anti asialo-GM1 antibody against NK cells and anti NK-1.1 monoclonal antibody (mAb to NKT cells abrogated the inhibitory action of JTT on lung metastasis of B16 melanoma cells. Although intraperitoneal administration of anti-IFN-γ mAb scarcely affected the inhibitory action of JTT on tumor cell metastasis, injection of amrinone, which used for IL-12 suppression, significantly decreased the ability of JTT to prevent tumor cell metastasis. These results strongly suggest that oral administration of JTT caused increase in the production of IL-12, which is responsible for the activation of both NK cell and NKT cell, in the lungs and results in inhibition of B16 melanoma cell metastasis in the lungs.

  9. Effect of hyperthermia alone and in combination with 60Co radiation of the growth of B16 melanoma in mice

    International Nuclear Information System (INIS)

    B16 melanoma was grown in the tail of B6D2F1/B0M mice. Procedures for simultaneous local 60C irradiation and heat treatment are described. A dose of 4 Gy has no effect on tumour growth; heat treatment of 41.50C for 200 min had a minor effect, while the combined treatment caused a marked delay in tumor growth. Heat treatment of tumours in the thigh at 41.50C for 2 hours did not influence the frequency of lung metastases. (Auth.)

  10. Adoptive Transfer of Tumor-Specific Tc17 Effector T Cells Controls the Growth of B16 Melanoma in Mice

    OpenAIRE

    de la Luz Garcia-Hernandez, Maria; Hamada, Hiromasa; Reome, Joyce B.; Misra, Sara K.; Tighe, Michael P.; Dutton, Richard W.

    2010-01-01

    In vitro generated OVA-specific IL-17–producing CD8 T effector cells (Tc17) from OT-1 mice, adoptively transferred into B16-OVA tumor-bearing mice, controlled tumor growth in early and late stage melanoma. IL-17, TNF, and IFN-γ from the Tc17 effectors all played a role in an enhanced recruitment of T cells, neutrophils, and macrophages to the tumor. In addition, Tc17 cells and recently recruited, activated neutrophils produced further chemokines, including CCL3, CCL4, CCL5, CXCL9, and CXCL10,...

  11. In vitro evaluation of low-intensity light radiation on murine melanoma (B16F10) cells.

    Science.gov (United States)

    Peidaee, P; Almansour, N M; Pirogova, E

    2016-03-01

    Changes in the energy state of biomolecules induced by electromagnetic radiation lead to changes in biological functions of irradiated biomolecules. Using the RRM approach, it was computationally predicted that far-infrared light irradiation in the range of 3500-6000 nm affects biological activity of proto-oncogene proteins. This in vitro study evaluates quantitatively and qualitatively the effects of selected far-infrared exposures in the computationally determined wavelengths on mouse melanoma B16F10 cells and Chinese hamster ovarian (CHO) cells by MTT (thiazolyl blue tetrazolium bromide) cell proliferation assay and confocal laser-scanning microscopy (CLSM). This paper also presents the findings obtained from irradiating B16F10 and CHO cells by the selected wavelengths in visible and near-infrared range. The MTT results show that far-infrared wavelength irradiation induces detrimental effect on cellular viability of B16F10 cells, while that of normal CHO cells is not affected considerably. Moreover, CLSM images demonstrate visible cellular detachment of cancer cells. The observed effects support the hypothesis that far-infrared light irradiation within the computationally determined wavelength range induces biological effect on cancer cells. From irradiation of selected visible and near-infrared wavelengths, no visible changes were detected in cellular viability of either normal or cancer cells. PMID:26002595

  12. Dual Role of Host Par2 in a Murine Model of Spontaneous Metastatic B16 Melanoma

    Czech Academy of Sciences Publication Activity Database

    Olejár, Tomáš; Větvička, D.; Zadinová, M.; Poučková, P.; Kukal, J.; Ježek, Petr; Matěj, R.

    2014-01-01

    Roč. 34, č. 7 (2014), s. 3511-3515. ISSN 0250-7005 R&D Projects: GA ČR(CZ) GAP302/10/0346 Institutional support: RVO:67985823 Keywords : PAR2 * melanoma * metastasis * murine model Subject RIV: EA - Cell Biology Impact factor: 1.826, year: 2014

  13. Oligoesculin fraction induces anti-tumor effects and promotes immune responses on B16-F10 mice melanoma.

    Science.gov (United States)

    Mokdad Bzeouich, Imen; Mustapha, Nadia; Sassi, Aicha; Ghedira, Kamel; Ghoul, Mohamed; Chebil, Latifa; Luis, José; Chekir-Ghedira, Leila

    2016-08-01

    Laccase was used to enzymatically polymerize esculin. Oligoesculin fraction was obtained after ultrafiltration through a 5-kDa membrane. Several studies have been carried out to prove the effectiveness of natural substances such as immunomodulators to promote the anti-cancer activity in situ. The purpose of our report was to explore whether the anti-tumor potential of the oligoesculin fraction in vitro and in vivo is linked to its immunological mechanisms in melanoma-bearing mice. We revealed that oligoesculin fraction reduced B16-F10 proliferation and migration in vitro in a dose-related manner. Moreover, melanin synthesis and tyrosinase activity were inhibited in these melanoma cells in a concentration-dependent way. The anti-tumor potential of oligoesculin fraction was also assessed in vivo. Our results showed that intraperitoneal administration of oligoesculin fraction, at 50 mg/kg body weight (b.w.) for 21 days, reduced tumor size and weight with percentages of inhibition of 94 and 87 %, respectively. Oligoesculin fraction was effective in promoting lysosomal activity and nitric oxide (NO) production by peritoneal macrophages in tumor-implanted mice. In addition, the activities of natural killer (NK), cytotoxic T lymphocytes, and macrophages were significantly enhanced by oligoesculin fraction. These findings suggested that this polymer with its anti-tumor and immunomodulatory properties could be used for the treatment of melanoma. PMID:26960691

  14. Reduced growth rate of tumors from melanoma B16 cells exposed to focused shock waves

    Czech Academy of Sciences Publication Activity Database

    Šunka, Pavel; Stelmashuk, Vitaliy; Beneš, J.; Poučková, P.

    Washington D.C: IEEE, 2007 - (Umstattd, R.), s. 494-497. (IEEE Conference proceedings). ISBN 978-1-4244-0018-8. [IEEE International Power Modulator Conference/2006./. Washington D.C. (US), 15.05.2006-19.05.2006] R&D Projects: GA ČR GA202/05/0685 Institutional research plan: CEZ:AV0Z20430508 Keywords : Shock waves * cavitaions * melanoma cells * reduced growthrate Subject RIV: BL - Plasma and Gas Discharge Physics

  15. Reduced growth rate of tumors from melanoma B16 cells exposed to focused shock waves

    Czech Academy of Sciences Publication Activity Database

    Šunka, Pavel; Stelmashuk, Vitaliy; Beneš, J.; Poučková, P.

    Piscataway: IEEE, 2007 - (Umstattd, R.), s. 494-497. (IEEE Catalog Number: 06CH37746). ISBN 978-1-4244-0018-8. ISSN 1930-885X. [2006 IEEE International Power Modulator Conference. Washington, DC (US), 15.05.2006-19.05.2006] R&D Projects: GA ČR GA202/05/0685 Institutional research plan: CEZ:AV0Z20430508 Keywords : Shock waves * cavitations * melanoma cells * tumor growth rate Subject RIV: BL - Plasma and Gas Discharge Physics

  16. Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).

    Science.gov (United States)

    Nakashima, Souichi; Oda, Yoshimi; Nakamura, Seikou; Liu, Jiang; Onishi, Koko; Kawabata, Miki; Miki, Hisako; Himuro, Yugo; Yoshikawa, Masayuki; Matsuda, Hisashi

    2015-07-01

    The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc

  17. A lectin from Bothrops leucurus snake venom raises cytosolic calcium levels and promotes B16-F10 melanoma necrotic cell death via mitochondrial permeability transition.

    Science.gov (United States)

    Aranda-Souza, Mary A; Rossato, Franco A; Costa, Rute A P; Figueira, Tiago R; Castilho, Roger F; Guarniere, Miriam C; Nunes, Erika S; Coelho, Luana C B B; Correia, Maria T S; Vercesi, Anibal E

    2014-05-01

    BlL, a galactose-binding C-type lectin purified from Bothrops leucurus snake venom, exhibits anticancer activity. The current study was designed to elucidate the cellular mechanisms by which BlL induces melanoma cell death. The viabilities of B16-F10 melanoma cells and HaCaT keratinocytes treated with BlL were evaluated. Necrotic and apoptotic cell death, cytosolic Ca(2+) levels, mitochondrial Ca(2+) transport and superoxide levels were assessed in B16-F10 melanoma cells exposed to BlL. We found that treatment with BlL caused dose-dependent necrotic cell death in B16-F10 melanoma cells. Conversely, the viability of non-tumorigenic HaCaT cells was not affected by similar doses of BlL. BlL-induced B16-F10 necrosis was preceded by a significant (2-fold) increase in cytosolic calcium concentrations and a significant (3-fold) increase in mitochondrial superoxide generation. It is likely that BlL treatment triggers B16-F10 cell death via mitochondrial permeability transition (MPT) pore opening because the pharmacological MPT inhibitors bongkrekic acid and Debio 025 greatly attenuated BlL-induced cell death. Experiments evaluating mitochondrial Ca(2+) transport in permeabilized B16-F10 cells strongly supported the hypothesis that BlL rapidly stimulates cyclosporine A-sensitive Ca(2+)-induced MPT pore opening. We therefore conclude that BlL causes selective B16-F10 melanoma cell death via dysregulation of cellular Ca(2+) homeostasis and Ca(2+)-induced opening of MPT pore. PMID:24593964

  18. Melanogenesis inhibitory activity of Korean Undaria pinnatifida in mouse B16 melanoma cells

    Directory of Open Access Journals (Sweden)

    Kim Min-Jin

    2014-06-01

    Full Text Available A number of seaweed species are used as traditional foods and medicine in different parts of the world, including Asian countries. However, very few data on the anti-melanogenic effect of seaweed have been published. Undaria pinnatifida (Dolmiyeok, a brown alga, is a traditional food in Jeju Island, the southern regions of the Korea peninsula. In this study, ethylacetate extracts of U. pinnatifida (UPE were examined for their anti-melanogenic potentials. Our results supports the finding that UPE down-regulated melanin content in a dose-dependent pattern. To clarify the target of UPE action in melanogenesis, we performed Western blotting for tyrosinase and microphthalmia-associated transcription factor (MITF, which are key melanogenic enzymes. UPE inhibited tyrosinase and MITF expressions in a dose-dependent manner. These results indicate that treatment with UPE significantly inhibits the melanogenesis in B16 cells, and may be effective in the whitening agent for the skin

  19. Cinnamomum cassia Essential Oil Inhibits α-MSH-Induced Melanin Production and Oxidative Stress in Murine B16 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Ying Shih

    2013-09-01

    Full Text Available Essential oils extracted from aromatic plants exhibit important biological activities and have become increasingly important for the development of aromatherapy for complementary and alternative medicine. The essential oil extracted from Cinnamomum cassia Presl (CC-EO has various functional properties; however, little information is available regarding its anti-tyrosinase and anti-melanogenic activities. In this study, 16 compounds in the CC-EO have been identified; the major components of this oil are cis-2-methoxycinnamic acid (43.06% and cinnamaldehyde (42.37%. CC-EO and cinnamaldehyde exhibited anti-tyrosinase activities; however, cis-2-methoxycinnamic acid did not demonstrate tyrosinase inhibitory activity. In murine B16 melanoma cells stimulated with α-melanocyte-stimulating hormone (α-MSH, CC-EO and cinnamaldehyde not only reduced the melanin content and tyrosinase activity of the cells but also down-regulated tyrosinase expression without exhibiting cytotoxicity. Moreover, CC-EO and cinnamaldehyde decreased thiobarbituric acid-reactive substance (TBARS levels and restored glutathione (GSH and catalase activity in the α-MSH-stimulated B16 cells. These results demonstrate that CC-EO and its major component, cinnamaldehyde, possess potent anti-tyrosinase and anti-melanogenic activities that are coupled with antioxidant properties. Therefore, CC-EO may be a good source of skin-whitening agents and may have potential as an antioxidant in the future development of complementary and alternative medicine-based aromatherapy.

  20. Hinokitiol Inhibits Melanogenesis via AKT/mTOR Signaling in B16F10 Mouse Melanoma Cells.

    Science.gov (United States)

    Tsao, Yu-Tzu; Huang, Yu-Fen; Kuo, Chun-Yu; Lin, Yu-Chiang; Chiang, Wei-Cheng; Wang, Wei-Kuang; Hsu, Chia-Wei; Lee, Che-Hsin

    2016-01-01

    H inokitiol purified from the heartwood of cupressaceous plants has had various biological functions of cell differentiation and growth. Hinokitiol has been demonstrated as having an important role in anti-inflammation and anti-bacteria effect, suggesting that it is potentially useful in therapies for hyperpigmentation. Previously, hinokitiol inhibited the production of melanin by inhibiting tyrosinase activity. The autophagic signaling pathway can induce hypopigmentation. This study is warranted to investigate the mechanism of hinokitiol-induced hypopigmentation through autophagy in B16F10 melanoma cells. The melanin contents and expression of microthphalmia associated transcription factor (MITF) and tyrosinase were inhibited by treatment with hinokitiol. Moreover, the phosphorylation of the protein express levels of phospho-protein kinase B (P-AKT) and phospho-mammalian targets of rapamycin (P-mTOR) were reduced after hinokitiol treatment. In addition, the microtubule associated protein 1 light chain 3 (LC3) -II and beclin 1 (autophagic markers) were increased after the B16F10 cell was treated with hinokitiol. Meanwhile, hinokitiol decreased cellular melanin contents in a dose-dependent manner. These findings establish that hinokitiol inhibited melanogenesis through the AKT/mTOR signaling pathway. PMID:26901194

  1. Cisplatin selectively downregulated the frequency and immunoinhibitory function of myeloid-derived suppressor cells in a murine B16 melanoma model.

    Science.gov (United States)

    Huang, Xiang; Cui, Shiyun; Shu, Yongqian

    2016-02-01

    The objective of this study was to investigate the immunomodulatory effect of cisplatin (DDP) on the frequency, phenotype and function of myeloid-derived suppressor cells (MDSC) in a murine B16 melanoma model. C57BL/6 mice were inoculated with B16 cells to establish the murine melanoma model and randomly received treatment with different doses of DDP. The percentages and phenotype of MDSC after DDP treatment were detected by flow cytometry. The immunoinhibitory function of MDSC was analyzed by assessing the immune responses of cocultured effector cells through CFSE-labeling assay, detection of interferon-γ production and MTT cytotoxic assay, respectively. Tumor growth and mice survival were monitored to evaluate the antitumor effect of combined DDP and adoptive cytokine-induced killer (CIK) cell therapy. DDP treatment selectively decreased the percentages, modulated the surface molecules and attenuated the immunoinhibitory effects of MDSC in murine melanoma model. The combination of DDP treatment and CIK therapy exerted synergistic antitumor effect against B16 melanoma. DDP treatment selectively downregulated the frequency and immunoinhibitory function of MDSC in B16 melanoma model, indicating the potential mechanisms mediating its immunomodulatory effect. PMID:26590944

  2. Influence of Fuse-2 Recipe on Mice B16 Melanoma Cells Tyrosinase%复色2号方对鼠黑素瘤B16细胞酪氨酸酶的影响

    Institute of Scientific and Technical Information of China (English)

    杨柳; 张明明; 马玲玲

    2012-01-01

    Objective; To explore molecular mechanism of fuse - 2 recipe on treating vitiligo. Methods; To determine the influence of fuse -2 recipe on B16 cell proliferation by MTT method, measuring and recording B16 cell proliferation by the microplate reader. To determine the influence of fuse -2 recipe on B16 cell tyrosines activity by tyrosinase DOPA rate oxidation method. To determine the melanin content of B16 cell by NaOH decomposition method. Results: There was no statistical significance(P >0.05)of fuse -2 drug concentration at 1 ~ lOOOg/L on B16 cell proliferation,but there was statistical significance (P <0. 05) on tyrosinase activity and melanin synthesis in a concentration dependent manner. Conclusion :Without effect on B16 melanoma cell proliferation, fuse -2 has a strong correlation effect during the dose on tyrosinase activity and melanin synthesis, which could achieve the goal of the treating vitiligo.%目的:探讨复色2号方治疗白癜风的分子学作用机制.方法:采用MTT法测定复色2号方对B16细胞增值的影响,在酶标仪下测定并记录B16细胞增殖情况;采用酪氨酸酶多巴速率氧化法测定复色2号方对酪氨酸酶活性的影响;采用NaOH裂解法测定B16细胞黑素含量.结果:复色2号方药物浓度在1~1000g/L对黑素瘤B16细胞增殖无统计学意义(P>0.05),但对酪氨酸酶活性和黑素合成有统计学意义(P<0.05),呈浓度依赖性.结论:复色2号方对黑素瘤B16细胞增殖无影响,但对酪氨酸酶活性和黑素合成有较强的剂量相关性促进作用,可以达到治疗白癜风的目的.

  3. BF-30 selectively inhibits melanoma cell proliferation via cytoplasmic membrane permeabilization and DNA-binding in vitro and in B16F10-bearing mice.

    Science.gov (United States)

    Wang, Hui; Ke, Mengyun; Tian, Yuwei; Wang, Jing; Li, Bing; Wang, Yizhou; Dou, Jie; Zhou, Changlin

    2013-05-01

    Cathelicidin-BF (BF-30) is a cathelicidin-like polypeptide composed of 30 amino acids and is a natural antibacterial peptide extracted from the venom of the snake Bungarus fasciatus. In our previous study, BF-30 showed broad antimicrobial activity against drug-resistant bacteria through enhancing the cytoplasmic membrane permeability. However, the anticancer activity of BF-30 has not yet been investigated. In this study, the effects of BF-30 on the proliferation of the metastatic melanoma cell line B16F10 in vitro and in vivo, as well as the mechanism were studied. Assay of cell viability, a B16F10-bearing mouse model, and histochemical examination were utilized to investigate the anti-tumor effects of BF-30. In addition, transmission electron microscope analysis, lactate dehydrogenase release assay, DNA retardation assay, Real-time PCR, Western blot, wound healing assay, and chick embryo chorioallantoic membrane assay were applied to elucidate the mechanism of BF-30 on B16F10. BF-30 inhibited B16F10 and B16 proliferation in vitro in a dose- and time-dependent manner with an IC50 of 7.3 µM and 13.9 µM, respectively. Moreover, BF-30 significantly suppressed melanoma growth in B16F10-bearing mice without body weight loss. The observed inhibition were 41.4%, 49.5% and 63.5% at the doses of 0.75, 1.5 and 3 mg/kg/day, respectively. This inhibition of metastatic melanoma cell proliferation was partially dependent on disrupting the cytoplasmic membrane, binding to genomic DNA, preventing transcription and translation of the VEGF gene. This inhibition restrained B16F10 migration and angiogenesis. These results further suggest that BF-30 may be a candidate for the treatment of malignant melanoma. PMID:23541725

  4. Hypo-pigmenting effect of sesquiterpenes from Inula britannica in B16 melanoma cells.

    Science.gov (United States)

    Choo, Soo-Jin; Ryoo, In-Ja; Kim, Kwan Chul; Na, Minkyun; Jang, Jae-Hyuk; Ahn, Jong Seog; Yoo, Ick-Dong

    2014-05-01

    During the course of screens to identify anti-melanogenic agents from natural resources, we found that the methanol extract of the dried flower of Inula britannica L. inhibited melanin synthesis in cultured melanoma cells stimulated with 3-isobutyl-1-methylxanthine (IBMX). A bioassay-guided isolation of the chloroform fraction of the I. britannica using an in vitro melanogenesis inhibition assay led to the isolation of sesquiterpenes, 1-O-acetylbritannilactone (1), britannilactone (2) and neobritannilactone B (3). Compounds 1 and 2 significantly reduced melanin production in a dose-dependent manner with IC50 values of 13.3 and 15.5 μM, respectively, whereas compound 3 was found to be cytotoxic. Compound 1 also inhibited the tyrosinase activity only in cell based-systems. Western blot analysis indicated that compound 1 inhibited melanogenesis by activating extracellular signal-regulated kinase (ERK) and Akt signaling and also inhibiting cAMP related binding protein, which regulates its downstream pathway, including tyrosinase, tyrosinase related protein-1 and TRP-2. These results demonstrated that compound 1, a major sesquiterpene from the flowers of I. britannica, exhibited anti-melanogenic activity by suppression of tyrosinase expression via ERK and Akt signaling. Taken together, our results suggest that these compounds may act as potent natural skin-lightening agents. PMID:24346861

  5. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    OpenAIRE

    Hesham Fahmy; Ahmed, Safwat A.; Szymanski, Pawel T.; Bhimanna Kuppast; Sherief Khalifa

    2011-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enh...

  6. Neem leaf glycoprotein optimizes effector and regulatory functions within tumor microenvironment to intervene therapeutically the growth of B16 melanoma in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Subhasis Barik

    2015-01-01

    Full Text Available Therapy with neem leaf glycoprotein (NLGP inhibits murine B16-melanoma in vivo and improves survivability. Studies on tumor-microenvironment (TME from NLGP treated mice (NLGP-TME suggests that anti-tumor effect is directly associated with enhanced CD8+T cell activity, dominance of type 1 cytokines/chemokine network with downregulation of suppressive cellular functions. NLGP-TME educated CD8+T cells showed higher perforin and granzymeB expression with greater in vitro cytotoxicity against B16 melanoma. These CD8+T cells showed proportionally lower FasR expression, denotes prevention from activation induced cell death by NLGP. Accumulated evidences strongly suggest NLGP influenced normalized TME allows CD8+T cells to perform optimally to inhibit melanoma growth.

  7. Arthrophytum scoparium inhibits melanogenesis through the down-regulation of tyrosinase and melanogenic gene expressions in B16 melanoma cells.

    Science.gov (United States)

    Chao, Hui-Chia; Najjaa, Hanen; Villareal, Myra O; Ksouri, Riadh; Han, Junkyu; Neffati, Mohamed; Isoda, Hiroko

    2013-02-01

    Melanin performs a crucial role in protecting the skin against harmful ultraviolet light. However, hyperpigmentation may lead to aesthetic problems and disorders such as solar lentigines (SL), melasma, postinflammatory hyperpigmentation and even melanoma. Arthrophytum scoparium grows in the desert in the North African region, and given this type of environment, A. scoparium exhibits adaptations for storing water and produces useful bioactive factors. In this study, the effect of A. scoparium ethanol extract (ASEE) on melanogenesis regulation in B16 murine melanoma cells was investigated. Cells treated with 0.017% (w/v) ASEE showed a significant inhibition of melanin biosynthesis in a time-dependent manner without cytotoxicity. To clarify the mechanism behind the ASEE-treated melanogenesis regulation, the expressions of tyrosinase enzyme and melanogenesis-related genes were determined. Results showed that the expression of tyrosinase enzyme was significantly decreased and Tyr, Trp-1, Mitf and Mc1R mRNA expressions were significantly down-regulated. LC-ESI-TOF-MS analysis of the extract identified the presence of six phenolic compounds: coumaric acid, cinnamic acid, chrysoeriol, cyanidin, catechol and caffeoylquinic acid. The melanogenesis inhibitory effect of ASEE may therefore be attributed to its catechol and tetrahydroisoquinoline derivative content. We report here that ASEE can inhibit melanogenesis in a time-dependent manner by decreasing the tyrosinase protein and Tyr, Trp-1, Mitf and Mc1R mRNA expressions. This is the first report on the antimelanogenesis effect of A. scoparium and on its potential as a whitening agent. PMID:23362872

  8. Vasoactive intestinal peptide stimulates melanogenesis in B16F10 mouse melanoma cells via CREB/MITF/tyrosinase signaling.

    Science.gov (United States)

    Yuan, Xing-Hua; Yao, Cheng; Oh, Jang-Hee; Park, Chi-Hyun; Tian, Yu-Dan; Han, Mira; Kim, Ji Eun; Chung, Jin Ho; Jin, Zhe-Hu; Lee, Dong Hun

    2016-08-26

    Vasoactive intestinal peptide (VIP), one of the major skin neuropeptides, has been suggested to have active roles in the pathogenesis of inflammatory skin disorders such as atopic dermatitis and psoriasis, which can commonly cause post-inflammatory hyperpigmentation. However, the effect of VIP on melanogenesis remains unknown. In this study, we showed that the melanin contents, tyrosinase activity, and gene expression of tyrosinase and microphthalmia-associated transcription factor (MITF) were significantly increased by treatment with VIP in B16F10 mouse melanoma cells and the stimulatory melanogenic effect was further examined in human epidermal melanocytes (HEMns). In addition, phosphorylated levels of CRE-binding protein (CREB) and protein kinase A (PKA) were markedly increased after VIP treatment, but not p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), or Akt, indicating the possible PKA-CREB signaling pathway involved in VIP-induced melanogenesis. This result was further verified by the fact that VIP induced increased melanin synthesis, and protein levels of phosphorylated CREB, MITF, tyrosinase were significantly attenuated by H89 (a specific PKA inhibitor). These data suggest that VIP-induced upregulation of tyrosinase through the CREB-MITF signaling pathway plays an important role in finding new treatment strategy for skin inflammatory diseases related pigmentation disorders. PMID:27343558

  9. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    Directory of Open Access Journals (Sweden)

    Hesham Fahmy

    2011-12-01

    Full Text Available Sarcodiol (SD is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3 and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4. SD treatment also enhances cellular level of tumor suppressor protein 53 (p53 and stimulates cleavage of the nuclear poly (ADP-ribose polymerase (cleaved-PARP. SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B16F10 tumor cells.

  10. Anti-tumour efficacy of mouse spleen cells separated with Dolichos biflorus lectin (DBA) in experimental pulmonary metastasis of B16 melanoma cells.

    OpenAIRE

    Okada, T.; Higuchi, M.; Takano, M; Maruyama, T.; Imai, Y; Osawa, T

    1990-01-01

    Anti-tumour effector cells were generated through 4 days culture of normal C57BL/6 splenocytes in a medium containing concanavalin A supernatant and then fractionated with Dolichos biflorus lectin (DBA) into DBA+ (agglutinable with DBA) and DBA- (non-agglutinable with DBA) cells. The DBA- cells, infused intravenously into mice together with B16 melanoma cells, or adoptively transferred into mice 3 days after the injection of B16 cells, caused a marked decrease in the number of lung nodules, w...

  11. Activation of MITF by Argan Oil Leads to the Inhibition of the Tyrosinase and Dopachrome Tautomerase Expressions in B16 Murine Melanoma Cells

    OpenAIRE

    Villareal, Myra O.; Sayuri Kume; Thouria Bourhim; Fatima Zahra Bakhtaoui; Kenichi Kashiwagi; Junkyu Han; Chemseddoha Gadhi; Hiroko Isoda

    2013-01-01

    Argan (Argania spinosa L.) oil has been used for centuries in Morocco as cosmetic oil to maintain a fair complexion and to cure skin pimples and chicken pox pustules scars. Although it is popular, the scientific basis for its effect on the skin has not yet been established. Here, the melanogenesis regulatory effect of argan oil was evaluated using B16 murine melanoma cells. Results of melanin assay using B16 cells treated with different concentrations of argan oil showed a dose-dependent decr...

  12. Melanoma in Organ Transplant Recipients: Incidence, Outcomes and Management Considerations

    OpenAIRE

    Ali, Faisal R; John T. Lear

    2012-01-01

    The incidence of melanoma continues to increase year on year. With better surgical techniques and medical management, greater numbers of organ transplants are being performed annually with much longer graft survival. The authors review our current understanding of the incidence of melanoma amongst organ transplant recipients, outcomes compared to the immunocompetent population, and management strategies in this burgeoning group.

  13. 姜辣素对小鼠 B16细胞黑素合成的影响%Effects of Gingerol on Melanogenesis of B16 Melanoma Cells

    Institute of Scientific and Technical Information of China (English)

    神芳丽; 霍仕霞

    2014-01-01

    Objective To study the effects of the gingerol on the melanogenesis in melanoma B16 cells. Methods Melanoma cells were cultured with gingerol at 12. 5, 25. 0, 50. 0, 100. 0, 200. 0 μmol · L-1 and positive control drug hydroquinone,respectively,using Dulbecco's modified eagle's medium(DMEM) as the blank control group. The cell proliferation was measured by methyl thiazolyltet tetrazolium ( MTT) colorimetric assay. The tyrosinase activity and melanin content were measured by colorimetry assay. Results Gingerol at different concentrations had inhibitory effect on B16 cell proliferation compared with the blank control group ( P 48%。与空白对照组比较,各浓度姜辣素均能够显著降低酪氨酸酶活性(P25.0μmol·L-1时,抑制黑素含量的水平基本无变化。结论姜辣素能有效抑制黑素细胞增殖和降低酪氨酸酶活性和黑素含量,从而减少黑素合成。

  14. The DNA intercalating alkaloid cryptolepine interferes with topoisomerase II and inhibits primarily DNA synthesis in B16 melanoma cells.

    Science.gov (United States)

    Bonjean, K; De Pauw-Gillet, M C; Defresne, M P; Colson, P; Houssier, C; Dassonneville, L; Bailly, C; Greimers, R; Wright, C; Quetin-Leclercq, J; Tits, M; Angenot, L

    1998-04-14

    Cryptolepine hydrochloride is an indoloquinoline alkaloid isolated from the roots of Cryptolepis sanguinolenta. It is characterized by a multiplicity of host-mediated biological activities, including antibacterial, antiviral, and antimalarial properties. To date, the molecular basis for its diverse biological effects remains largely uncertain. Several lines of evidence strongly suggest that DNA might correspond to its principal cellular target. Consequently, we studied the strength and mode of binding to DNA of cryptolepine by means of absorption, fluorescence, circular, and linear dichroism, as well as by a relaxation assay using DNA topoisomerases. The results of various optical and gel electrophoresis techniques converge to reveal that the alkaloid binds tightly to DNA and behaves as a typical intercalating agent. In DNAase I footprinting experiments it was found that the drug interacts preferentially with GC-rich sequences and discriminates against homo-oligomeric runs of A and T. This study has also led to the discovery that cryptolepine is a potent topoisomerase II inhibitor and a promising antitumor agent. It stabilizes topoisomerase II-DNA covalent complexes and stimulates the cutting of DNA at a subset of preexisting topoisomerase II cleavage sites. Taking advantage of the fluorescence of the indoloquinoline chromophore, fluorescence microscopy was used to map cellular uptake of the drug. Cryptolepine easily crosses the cell membranes and accumulates selectively into the nuclei rather than in the cytoplasm of B16 melanoma cells. Quantitative analyses of DNA in cells after Feulgen reaction and image cytometry reveal that the drug blocks the cell cycle in G2/M phases. It is also shown that the alkaloid is more potent at inhibiting DNA synthesis rather than RNA and protein synthesis. Altogether, the results provide direct evidence that DNA is the primary target of cryptolepine and suggest that this alkaloid is a valid candidate for the development of tumor

  15. Escherichia coli Nissle 1917 Targets and Restrains Mouse B16 Melanoma and 4T1 Breast Tumors through Expression of Azurin Protein

    OpenAIRE

    Zhang, Yunlei; Zhang, Youming; Xia, Liqiu; Zhang, XiangLi; Ding, Xuezhi; Yan, Fu; Wu, Feng

    2012-01-01

    Many studies have demonstrated that intravenously administered bacteria can target and proliferate in solid tumors and then quickly be released from other organs. Here, we employed the tumor-targeting property of Escherichia coli Nissle 1917 to inhibit mouse B16 melanoma and 4T1 breast tumors through the expression of azurin protein. For this purpose, recombinant azurin-expressing E. coli Nissle 1917 was developed. The levels of in vitro and in vivo azurin secretion in the engineered bacteriu...

  16. BFD-22 a new potential inhibitor of BRAF inhibits the metastasis of B16F10 melanoma cells and simultaneously increased the tumor immunogenicity.

    Science.gov (United States)

    Ferreira, Adilson Kleber; Pasqualoto, Kerly Fernanda Mesquita; Kruyt, Frank A E; Palace-Berl, Fanny; Azevedo, Ricardo Alexandre; Turra, Kely Medeiros; Rodrigues, Cecilia Pessoa; Ferreira, Ana Carolina Franco; Salomón, Maria Alejandra Clavijo; de Sá Junior, Paulo Luiz; Farias, Camyla Fernandes; Figueiredo, Carlos Rogerio; Tavares, Leoberto Costa; Barbuto, José Alexandre Marzagão; Jorge, Salomão Dória

    2016-03-15

    Benzofuroxan is an interesting ring system, which has shown a wide spectrum of biological responses against tumor cell lines. We investigated, herein, the antitumor effects of benzofuroxan derivatives (BFDs) in vitro and in a melanoma mouse model. Cytotoxic effects of twenty-two BFDs were determined by MTT assay. Effects of BFD-22 in apoptosis and cell proliferation were evaluated using Annexin V-FITC/PI and CFSE staining. In addition, the effects in the cell cycle were assessed. Flow cytometry, western blot, and fluorescence microscopy analysis were employed to investigate the apoptosis-related proteins and the BRAF signaling. Cell motility was also exploited through cell invasion and migration assays. Molecular docking approach was performed in order to verify the BFD-22 binding mode into the ATP catalytic site of BRAF kinase. Moreover, the BFD-22 antitumor effects were evaluated in a melanoma murine model using B16F10. BFD-22 was identified as a potential hit against melanoma cells. BFD-22 induced apoptosis and inhibited cell proliferation of B16F10 cells. BFD-22 has suppressed, indeed, the migratory and invasive behavior of B16F10 cells. Cyclin D1 and CDK4 expression were reduced leading to cell cycle arrest at G0/G1 phase. Of note, phosphorylation of BRAF at Ser338 was strongly down-regulated by BFD-22 in B16F10 cells. The accommodation/orientation into the binding site of BRAF was similar of BAY43-9006 (co-crystallized inhibitor of BRAF, sorafenib). Importantly, BFD-22 presented in vivo antimetastatic effects and showed better therapeutic efficacy than sorafenib and taxol. BFD-22 can be considered as a new lead compound and, then, can be helpful for the designing of novel drug candidates to treat melanoma. PMID:26876618

  17. Antitumor Effects In Vitro and In Vivo and Mechanisms of Protection against Melanoma B16F10-Nex2 Cells By Fastuosain, a Cysteine Proteinase from Bromelia fastuosa

    OpenAIRE

    Guimarães-Ferreira, Carla A; Rodrigues, Elaine G; Renato A Mortara; Hamilton Cabral; Fabiana A. Serrano; Ricardo Ribeiro-dos-Santos; Travassos, Luiz R.

    2007-01-01

    In the present work, the antitumor effect of fastuosain, a cysteine proteinase from Bromelia fastuosa, was investigated. In the intravenous model of lung colonization in C57BI/6 mice, fastuosain and bromelain injected intraperitoneally were protective, very few nodules of B16F10-Nex2 melanoma cells were detected. Tumor cells treated with fastuosain showed reduced expression of CD44 and decreased invasion through Matrigel, lost their cytoplasmic extensions and substrate adherence, became round...

  18. Compounds isolated from the aerial part of Crataegus azarolus inhibit growth of B16F10 melanoma cells and exert a potent inhibition of the melanin synthesis.

    Science.gov (United States)

    Mustapha, Nadia; Bzéouich, Imèn Mokdad; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2015-02-01

    Poor therapeutic results have been reported for treatment of malignant melanoma; therefore in this study, we have investigated inhibitory capacity of vitexin-2''-O-rhamnoside as well as the extract from which it was isolated, i.e. the ethyl acetate extract obtained from the leaves of Crataegus azarolus, on mouse melanoma (B16F10) proliferation. Cell viability was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, amounts of melanin and tyrosinase were measured spectrophotometrically at 475nm. Ethyl acetate extract and vitexin-2''-O-rhamnoside exhibited significant anti-proliferative activity against B16F10 melanoma cells after incubation for 48hours with IC50s of 50μg/mL and 20μM, respectively. Furthermore, these two compounds have the ability to reduce the melanin content by inhibiting the tyrosinase activity of B16F10 cells. Thus, further investigations are merited to ascertain their potential application in treating hyperpigmentation disorders. PMID:25661350

  19. Enhancement of pEgr-p16 expression induced by irradiation and its anti-tumor effect on B16 melanoma cells in vitro

    International Nuclear Information System (INIS)

    Objective: To study the antitumour effect of irradiation combination with recombined pEgr-p16 plasmid on melanoma B16 cells. Methods: pEgr-p16 plasmids were transfected into B16 cell line. Quantitative RT-PCR, flow cytometry and MTT methods were used to detect the expression of p16, cell apoptosis and inhibition effect, respectively. Results: The p16 expressions in different doses X-ray irradiation group were about 3.78-6.67 times higher than that in sham-irradiation group (P<0.01). The expressions of p16 gradually increased with time after exposure to 2 Gy X-ray irradiation and reached to maximum at 72 h. Apoptosis rate in transfected p16 combined with irradiation group was higher than that in either plasmid or irradiation group alone (P<0.05-0.01). The number of pEgr-p16-transfected B16 cells exposed to 2 Gy X-ray irradiation was significantly less than those in other experimental groups (P<0.05-0.001). Conclusions: pEgr-p16 gene transfection combined with irradiation could suppress melanoma B16 cell growth. And the inhibition was more effective than those in gene- or irradiation-therapy alone. (authors)

  20. The Mechanism of Medium Stimulating the Melanin Synthesis in B16 Murine Melanoma Cells%培养基诱导B16细胞黑色素合成及机理研究

    Institute of Scientific and Technical Information of China (English)

    陈金妹; 林进妹; 黄家福; 欧一新; 曹娜; 张秀芬; 朱祯慧; 潘裕添

    2016-01-01

    研究不同培养基对B16细胞体外培养生物学特性的影响及其黑色素表达能力与相关分子作用机制。方法:利用不同培养基对B16细胞进行体外连续传代培养,考查培养基对细胞形态、细胞成活率、细胞周期和黑色素合成等方面的影响。同时,借助RT-PCR、Western Blot和双向电泳等技术,研究与黑色素生物合成相关蛋白质的表达水平。结果:B16细胞在Gibco-RPMI-1640-31800和Gibco-DMEM-12800这两种培养基中培养时,细胞外观形态良好、细胞活力强、传代周期短并且均可稳定连续传代培养,两者的细胞周期也一致;B16细胞在Gibco-RPMI-1640-31800培养基中基本不合成黑色素,而在Gibco-DMEM-12800培养基能大量合成黑色素。分析B16细胞中三种黑色素合成相关蛋白质(Tyrosinase,Tyrosinase-related protein 1和Tyrosinase-related protein 2)在以上两种培养基中表达的差异,发现这三种蛋白质的mRNA转录水平基本没有差异,在Gibco-DMEM-12800培养基中这三种蛋白质的翻译水平均明显提高,总蛋白质组也更加多样。结论:Gibco-DMEM-12800培养基通过提高Tyrosinase、TRP1和TRP2等三种蛋白质的翻译水平使B16细胞黑色素大量合成。%To study the effect of different media on the biological characteristics of B16 murine melanoma cells in vitro, and the expression mechanism of melanin, B16 cells were subcultured continuously in different media, and their biological characteristics including morphology, cell proliferation, cell cycle were observed. Meanwhile, the transcriptional and translational levels of melanin were investigated by Western Blot, RT-PCR, and two-dimensional electrophoresis. The results indicated that B16 murine melanoma cells had good cellular morphology, high cell viability, rapid proliferation, and could be subcultured continuously in two media, Gibco-RPMI-1640-31800 (RPMI-1640) and Gibco-DMEM-12800 (DMEM). However, melanin

  1. Carnosic acid inhibits the epithelial-mesenchymal transition in B16F10 melanoma cells: a possible mechanism for the inhibition of cell migration.

    Science.gov (United States)

    Park, So Young; Song, Hyerim; Sung, Mi-Kyung; Kang, Young-Hee; Lee, Ki Won; Park, Jung Han Yoon

    2014-01-01

    Carnosic acid is a natural benzenediol abietane diterpene found in rosemary and exhibits anti-inflammatory, antioxidant, and anti-carcinogenic activities. In this study, we evaluated the effects of carnosic acid on the metastatic characteristics of B16F10 melanoma cells. When B16F10 cells were cultured in an in vitro Transwell system, carnosic acid inhibited cell migration in a dose-dependent manner. Carnosic acid suppressed the adhesion of B16F10 cells, as well as the secretion of matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, urokinase plasminogen activator (uPA), and vascular cell adhesion molecule (VCAM)-1. Interestingly, secretion of TIMP-2 increased significantly in B16F10 cells treated with 10 μmol/L carnosic acid. Additionally, carnosic acid suppressed the mesenchymal markers snail, slug, vimentin, and N-cadherin and induced epithelial marker E-cadherin. Furthermore, carnosic acid suppressed phosphorylation of Src, FAK, and AKT. These results indicate that inhibition of the epithelial-mesenchymal transition may be important for the carnosic acid-induced inhibition of B16F10 cell migration. PMID:25036034

  2. Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax®

    Directory of Open Access Journals (Sweden)

    Korets-Smith Ella

    2007-04-01

    Full Text Available Abstract Background Melanoma tumors are known to express antigens that usually induce weak immune responses of short duration. Expression of both tumor-associated antigens p53 and TRP2 by melanoma cells raises the possibility of simultaneously targeting more than one antigen in a therapeutic vaccine. In this report, we show that VacciMax® (VM, a novel liposome-based vaccine delivery platform, can increase the immunogenicity of melanoma associated antigens, resulting in tumor elimination. Methods C57BL/6 mice bearing B16-F10 melanoma tumors were vaccinated subcutaneously 6 days post tumor implantation with a mixture of synthetic peptides (modified p53: 232–240, TRP-2: 181–188 and PADRE and CpG. Tumor growth was monitored and antigen-specific splenocyte responses were assayed by ELISPOT. Results Vaccine formulated in VM increased the number of both TRP2- and p53-specific IFN-γ producing splenocytes following a single vaccination. Vaccine formulated without VM resulted only in enhanced IFN-γ producing splenocytes to one CTL epitopes (TRP2:180–188, suggesting that VM overcomes antigen dominance and enhances immunogenicity of multiple epitopes. Vaccination of mice bearing 6-day old B16-F10 tumors with both TRP2 and p53-peptides formulated in VM successfully eradicated tumors in all mice. A control vaccine which contained all ingredients except liposomes resulted in eradication of tumors in no more than 20% of mice. Conclusion A single administration of VM is capable of inducing an effective CTL response to multiple tumor-associated antigens. The responses generated were able to reject 6-day old B16-F10 tumors.

  3. Bioactive Constituents of Zanthoxylum rhetsa Bark and Its Cytotoxic Potential against B16-F10 Melanoma Cancer and Normal Human Dermal Fibroblast (HDF) Cell Lines.

    Science.gov (United States)

    Santhanam, Ramesh Kumar; Ahmad, Syahida; Abas, Faridah; Safinar Ismail, Intan; Rukayadi, Yaya; Tayyab Akhtar, Muhammad; Shaari, Khozirah

    2016-01-01

    Zanthoxylum rhetsa is an aromatic tree, known vernacularly as "Indian Prickly Ash". It has been predominantly used by Indian tribes for the treatment of many infirmities like diabetes, inflammation, rheumatism, toothache and diarrhea. In this study, we identified major volatile constituents present in different solvent fractions of Z. rhetsa bark using GC-MS analysis and isolated two tetrahydrofuran lignans (yangambin and kobusin), a berberine alkaloid (columbamine) and a triterpenoid (lupeol) from the bioactive chloroform fraction. The solvent fractions and purified compounds were tested for their cytotoxic potential against human dermal fibroblasts (HDF) and mouse melanoma (B16-F10) cells, using the MTT assay. All the solvent fractions and purified compounds were found to be non-cytotoxic to HDF cells. However, the chloroform fraction and kobusin exhibited cytotoxic effect against B16-F10 melanoma cells. The presence of bioactive lignans and alkaloids were suggested to be responsible for the cytotoxic property of Z. rhetsa bark against B16-F10 cells. PMID:27231889

  4. Redox-Active Profile Characterization of Remirea maritima Extracts and It Cytotoxic Effect in Mouse Fibroblasts (L929 and Melanoma (B16F10 Cells

    Directory of Open Access Journals (Sweden)

    Grace Anne A. Dória

    2015-06-01

    Full Text Available Remirea maritima is a tropical plant with a reticulated root system belonging to the family Cyperaceae, also known to have biologically active secondary metabolites. However, very few data on R. maritima’s biological actions are available and there are no reports regarding the redox-active profile of this plant. In this study, we examined the total phenolic content of Remirea maritima hydroalcoholic (RMHA extracts, redox properties against different reactive species generated in vitro and their cytotoxic effect against fibroblasts (L929 and melanoma (B16F10 cells. Total reactive antioxidant potential index (TRAP and total antioxidant reactivity (TAR results revealed that RMHA at all concentrations tested showed significant antioxidant capacity. RMHA was also effective against hydroxyl radical formation, reduction of Fe3+ to Fe2+ and in scavenging nitric oxide (NO radicals. In vitro, the level of lipid peroxidation was reduced by RMHA extract and the data showed significant oxidative damage protection. The RMHA cytotoxicity was evaluated by a neutral red assay in fibroblast (L929 and melanome (B16F10 cells. The obtained results showed that the RMHA (40 and 80 µg/mL, respectively reduced 70% of the viable cells. In conclusion, this study represents the first report regarding the antioxidant and anti-proliferative potential of R. maritima against B16F10 melanoma cells.

  5. Inhibitory effects of ethyl acetate extract of Cordyceps sinensis mycelium on various cancer cells in culture and B16 melanoma in C57BL/6 mice.

    Science.gov (United States)

    Wu, Jian Yong; Zhang, Qiao Xia; Leung, Po Hong

    2007-01-01

    The cultivated mycelium of a Cordyceps sinensis (Cs) fungus was sequentially extracted by petroleum ether (PE), ethyl acetate (EtOAc), ethanol (EtOH) and hot water. All solvent extracts except hot water extract showed a significant and dose-dependent inhibitory effect on the proliferation of four cancer cell lines, MCF-7 breast cancer, B16 mouse melanoma, HL-60 human premyelocytic leukemia and HepG2 human hepatocellular carcinoma, with IC(50) values below 132 microg/ml. The EtOAc extract, in particular, had the most potent effect against all four cancer cell lines, with IC(50) between 12 microg/ml (on B16) and 45 microg/ml (on MCF-7). In contrast, it had much lower cytotoxicity against normal mouse bone marrow cells. The EtOAc extract contained carbohydrates, adenosine, ergosterol and trace amount of cordycepin, of which ergosterol and related compounds were identified as a major class of active constituents contributing to the in vitro cytotoxicity. In an animal test, the EtOAc extract showed significant inhibiting effect on B16-induced melanoma in C57BL/6 mice, causing about 60% decrease of tumor size over 27 days. Our results suggest that the EtOAc extract of Cs fungal mycelium has strong anti-tumor activity and is a potential source of natural anti-tumor products. PMID:16423520

  6. Bioactive Constituents of Zanthoxylum rhetsa Bark and Its Cytotoxic Potential against B16-F10 Melanoma Cancer and Normal Human Dermal Fibroblast (HDF Cell Lines

    Directory of Open Access Journals (Sweden)

    Ramesh Kumar Santhanam

    2016-05-01

    Full Text Available Zanthoxylum rhetsa is an aromatic tree, known vernacularly as “Indian Prickly Ash”. It has been predominantly used by Indian tribes for the treatment of many infirmities like diabetes, inflammation, rheumatism, toothache and diarrhea. In this study, we identified major volatile constituents present in different solvent fractions of Z. rhetsa bark using GC-MS analysis and isolated two tetrahydrofuran lignans (yangambin and kobusin, a berberine alkaloid (columbamine and a triterpenoid (lupeol from the bioactive chloroform fraction. The solvent fractions and purified compounds were tested for their cytotoxic potential against human dermal fibroblasts (HDF and mouse melanoma (B16-F10 cells, using the MTT assay. All the solvent fractions and purified compounds were found to be non-cytotoxic to HDF cells. However, the chloroform fraction and kobusin exhibited cytotoxic effect against B16-F10 melanoma cells. The presence of bioactive lignans and alkaloids were suggested to be responsible for the cytotoxic property of Z. rhetsa bark against B16-F10 cells.

  7. Redox-Active Profile Characterization of Remirea maritima Extracts and Its Cytotoxic Effect in Mouse Fibroblasts (L929) and Melanoma (B16F10) Cells.

    Science.gov (United States)

    Dória, Grace Anne A; Santos, Anderson R; Bittencourt, Leonardo S; Bortolin, Rafael C; Menezes, Paula P; Vasconcelos, Bruno S; Souza, Rebeca O; Fonseca, Maria José V; Santos, Alan Diego C; Saravanan, Shanmugam; Silva, Francilene A; Gelain, Daniel P; Moreira, José Cláudio F; Prata, Ana Paula N; Quintans-Júnior, Lucindo J; Araújo, Adriano A S

    2015-01-01

    Remirea maritima is a tropical plant with a reticulated root system belonging to the family Cyperaceae, also known to have biologically active secondary metabolites. However, very few data on R. maritima's biological actions are available and there are no reports regarding the redox-active profile of this plant. In this study, we examined the total phenolic content of Remirea maritima hydroalcoholic (RMHA) extracts, redox properties against different reactive species generated in vitro and their cytotoxic effect against fibroblasts (L929) and melanoma (B16F10) cells. Total reactive antioxidant potential index (TRAP) and total antioxidant reactivity (TAR) results revealed that RMHA at all concentrations tested showed significant antioxidant capacity. RMHA was also effective against hydroxyl radical formation, reduction of Fe3+ to Fe2+ and in scavenging nitric oxide (NO) radicals. In vitro, the level of lipid peroxidation was reduced by RMHA extract and the data showed significant oxidative damage protection. The RMHA cytotoxicity was evaluated by a neutral red assay in fibroblast (L929) and melanome (B16F10) cells. The obtained results showed that the RMHA (40 and 80 µg/mL, respectively) reduced 70% of the viable cells. In conclusion, this study represents the first report regarding the antioxidant and anti-proliferative potential of R. maritima against B16F10 melanoma cells. PMID:26121396

  8. Antitumor Effects In Vitro and In Vivo and Mechanisms of Protection against Melanoma B16F10-Nex2 Cells By Fastuosain, a Cysteine Proteinase from Bromelia fastuosa

    Directory of Open Access Journals (Sweden)

    Carla A. Guimarães-Ferreira

    2007-09-01

    Full Text Available In the present work, the antitumor effect of fastuosain, a cysteine proteinase from Bromelia fastuosa, was investigated. In the intravenous model of lung colonization in C57BI/6 mice, fastuosain and bromelain injected intraperitoneally were protective, very few nodules of B16F10-Nex2 melanoma cells were detected. Tumor cells treated with fastuosain showed reduced expression of CD44 and decreased invasion through Matrigel, lost their cytoplasmic extensions and substrate adherence, became round and detached, forming strongly bound cell clusters in suspension. Peritoneal cells recruited and activated by fastuosain treatment (mainly monocytic cells and lymphocytes migrated to the lung, where pulmonary melanoma metastases grew. Adoptive transference of peritoneal cells recruited by fastuosain had no protective effect against lung metastases in recipient mice. Treatment of green fluorescent protein -chimeric animals with fastuosain did not change the number of cells that migrated to the lung, compared to PBSinjected control mice, but the number of positive major histocompatibility complex class II cells increased with fastuosain treatment. Murine antibodies against fastuosain, bromelain, cathepsins B and L crossreacted in ELISA and recognized surface and cytoplasmic components expressed on B16F10-Nex2 cells. Anti-fastuosain antibodies were cytotoxic/lytic to B16F10-Nex2 cells. Antitumor effects of fastuosain involve mainly the direct effect of the enzyme and elicitation of protective antibodies.

  9. Antiproliferative activity and apoptosis induction of Eucalyptus Citriodora resin and its major bioactive compound in melanoma B16F10 cells.

    Science.gov (United States)

    Duh, Pin-Der; Chen, Zong-Tsi; Lee, Shwu-Woan; Lin, Tsuey-Pin; Wang, Ya-Ting; Yen, Wen-Jye; Kuo, Ling-Feng; Chu, Heuy-Ling

    2012-08-15

    Antiproliferative activity and apoptosis induction of ethyl acetate of Eucalyptus citriodora resin (EAEER), and its major bioactive compound in melanoma B16F10 cells were investigated. 6-[1-(p-Hydroxy-phenyl)ethyl]-7-O-methyl aromadendrin (HEMA), a flavanol derivative, was isolated from EAEER and identified on the basis of its mass and NMR spectra. The results from MTT assay showed high antiproliferative effects of EAEER and HEMA on B16F10 cells. Moreover, EAEER- and HEMA-induced cell apoptosis was association with the decrease in the mitochondrial transmembrane potentials (Δψ(m)), increase in Bax/Bcl-2 ratio, and activation of caspase-3. Cells treated with EAEER and HEMA generated intracellular reactive oxygen species (ROS) and nitric oxide (NO), indicating that ROS and RNS play important roles in the induction of apoptosis in B16F10 cells. Taken together, EAEER and its major bioactive compound, HEMA, inhibited the proliferation of B16F10 cells via apoptosis and may be a potential antimelanoma agent. PMID:22838509

  10. Inhibition effect of phenyl compounds from the Oryza sativa roots on melanin production in murine B16-F10 melanoma cells.

    Science.gov (United States)

    Cho, Jin-Gyeong; Huh, Jeongran; Jeong, Rak-Hun; Cha, Byeong-Ju; Shrestha, Sabina; Lee, Dong-Geol; Kang, Hee-Cheol; Kim, Ji-Young; Baek, Nam-In

    2015-01-01

    Five phenyl compounds, vanillin (1), methyl trans-ferulate (2), trans-p-coumaric acid methyl ester (3), N-benzoyltryptamine (4), and N-(trans-cinnamoyl)tryptamine (5), were isolated from the roots of Oryza sativa L. and identified on the basis of spectroscopic data. Compounds 3 and 5 showed strong inhibition effect on melanin production in murine B16-F10 melanoma cells and tyrosinase activity. Also, the quantitative analysis of the compounds was carried out using LC/MS/MS experiment. Compounds 3 and 5 could be used as skin-whitening agents. PMID:25299734

  11. Effects of L-DOPA pre-loading on the uptake of boronophenylalanine using the F98 glioma and B16 melanoma models

    International Nuclear Information System (INIS)

    The present study was undertaken to evaluate the effects of L-DOPA pre-loading on the uptake of BPA using the F98 rat glioma and the murine B16 melanoma models. In vitro pretreatments of F98 glioma and B16 melanoma cells with L-DOPA, followed by exposure to BPA increased boron uptake, as determined by inductively coupled plasma-optical emission spectroscopy (ICP-OES). Based on this, in vivo studies were initiated in F98 glioma bearing rats. Initially, the L-DOPA dosing paradigm was evaluated. Maximum tumor boron uptake was observed following i.p. administration of L-DOPA (50 mg/kg) followed 24 h later by BPA (31.8±8.9 vs. 17.2±6.3 µg/g for BPA alone). Next, the effect of L-DOPA pre-loading as a function of the route of administration of BPA was evaluated in F98 glioma bearing rats. The greatest increase in uptake was seen following i.v. administration of BPA, while in contrast no significant increase was seen following intracarotid (i.c.) administration (38.6±12.4 vs. 34.2±10.9). Cellular localization of the F98 glioma, as determined by secondary ion mass spectrometry (SIMS) boron imaging revealed equivalent tumor boron concentrations following L-DOPA pre-loading. In vivo studies in B16 melanoma bearing mice showed equivalent tumor boron values in treated and untreated mice, suggesting that the effects of L-DOPA pre-loading may depend both on the histologic type of tumor and its anatomic site. - Highlights: • Effects of L-DOPA pre-loading on the uptake of BPA were studied using the F98 glioma and B16 melanoma models. • In vitro studies using both cell lines revealed that pre-loading resulted in increased uptake of BPA. • Enhanced uptake of BPA was seen following i.v. administration to F98 glioma bearing rats (31.8 vs. 17.2 µg/g). • The effects of L-DOPA pre-loading may depend both on the histologic type of tumor and its anatomic site

  12. Paullinia cupana Mart var. sorbilis, guaraná, reduces cell proliferation and increases apoptosis of B16/F10 melanoma lung metastases in mice

    OpenAIRE

    Fukumasu, H.; J.L. Avanzo; Nagamine, M.K.; J.A. Barbuto; Rao, K.V.; M.L.Z. Dagli

    2008-01-01

    We showed that guaraná (Paullinia cupana Mart var. sorbilis) had a chemopreventive effect on mouse hepatocarcinogenesis and reduced diethylnitrosamine-induced DNA damage. In the present experiment, we evaluated the effects of guaraná in an experimental metastasis model. Cultured B16/F10 melanoma cells (5 x 10(5) cells/animal) were injected into the tail vein of mice on the 7th day of guaraná treatment (2.0 mg P. cupana/g body weight, per gavage) and the animals were treated with guaraná daily...

  13. Electrotransfer of Plasmid DNA Encoding an Anti-Mouse Endoglin (CD105 shRNA to B16 Melanoma Tumors with Low and High Metastatic Potential Results in Pronounced Anti-Tumor Effects

    Directory of Open Access Journals (Sweden)

    Tanja Dolinsek

    2015-12-01

    Full Text Available Endoglin overexpression is associated with highly proliferative tumor endothelium and also with some tumors, including melanoma. Its targeting has anti-tumor effectiveness, which can also be obtained by RNA interference. The aim of our study was to explore the anti-tumor effectiveness of endoglin silencing by electrotransfer of plasmid DNA encoding short hairpin RNA against endoglin in two murine B16 melanoma variants with different metastatic potential on cells, spheroids and subcutaneous tumors in mice. The results demonstrate that endoglin silencing with gene electrotransfer reduces the proliferation, survival and migration of melanoma cells and also has anti-tumor effectiveness, as the therapy resulted in a high percentage of tumor cures (23% and 58% on B16F1 and B16F10 tumors, respectively. The effectiveness of the therapy correlated with endoglin expression in melanoma cells; in vitro the effects were more pronounced in B16F1 cells, which express more endoglin than B16F10. However, the opposite was observed in vivo in tumors, where there was a higher expression of endoglin and better anti-tumor effectiveness in the B16F10 tumor. In conclusion, targeting endoglin for the treatment of melanoma seems to be a concept worthy of further exploration due to the increased therapeutic effect of the therapy based on simultaneous vascular targeting and its direct effect on tumor cells.

  14. Escherichia coli Nissle 1917 targets and restrains mouse B16 melanoma and 4T1 breast tumors through expression of azurin protein.

    Science.gov (United States)

    Zhang, Yunlei; Zhang, Youming; Xia, Liqiu; Zhang, Xiangli; Ding, Xuezhi; Yan, Fu; Wu, Feng

    2012-11-01

    Many studies have demonstrated that intravenously administered bacteria can target and proliferate in solid tumors and then quickly be released from other organs. Here, we employed the tumor-targeting property of Escherichia coli Nissle 1917 to inhibit mouse B16 melanoma and 4T1 breast tumors through the expression of azurin protein. For this purpose, recombinant azurin-expressing E. coli Nissle 1917 was developed. The levels of in vitro and in vivo azurin secretion in the engineered bacterium were determined by immunochemistry. Our results demonstrated that B16 melanoma and orthotopic 4T1 breast tumor growth were remarkably restrained and pulmonary metastasis was prevented in immunocompetent mice. It is worth noting that this therapeutic effect partially resulted from the antitumor activity of neutrophils and lymphocytes due to inflammatory responses caused by bacterial infections. No toxicity was observed in the animal during the experiments. This study indicates that E. coli Nissle 1917 could be a potential carrier to deliver antitumor drugs effectively for cancer therapy. PMID:22923405

  15. Comparative Depigmentation Effects of Resveratrol and Its Two Methyl Analogues in α-Melanocyte Stimulating Hormone-Triggered B16/F10 Murine Melanoma Cells.

    Science.gov (United States)

    Yoon, Hoon-Seok; Hyun, Chang-Gu; Lee, Nam-Ho; Park, Sung-Soo; Shin, Dong-Bum

    2016-06-01

    Previous research showed that resveratrol (trans-3,4',5-trihydroxystilbene) and pinostilbene (trans-3-methoxy-4',5-dihydroxystilbene) were able to inhibit tyrosinase directly; however, anti-melanogenic effects of pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene) and resveratrol trimethyl ether (RTE) have not been compared. To investigate the hypopigmentation effects of pterostilbene and RTE, melanin contents and intracellular tyrosinase activity were determined by western blot analysis. Firstly, pterostilbene showed the inhibitory effects on α-melanocyte stimulating hormone (MSH)-induced melanin synthesis stronger than RTE, resveratrol, and arbutin. Pterostilbene inhibited melanin biosynthesis in a dose-dependent manner in α-MSH-stimulated B16/F10 murine melanoma cells. Specifically, melanin content and intracellular tyrosinase activity were inhibited by 63% and 58%, respectively, in response to treatment with 10 μM of pterostilbene. The results of western blot analysis indicated that pterostilbene induced downregulation of tyrosinase protein expression and suppression of α-MSH-stimulated melan-A protein expression stronger than RTE or resveratrol. Based on these results, our study suggests that pterostilbene can induce hypopigmentation effects more effectively than resveratrol and RTE, and it functions via downregulation of protein expression associated with hyperpigmentation in α-MSH-triggered B16/F10 murine melanoma cells. PMID:27390733

  16. Comparative Depigmentation Effects of Resveratrol and Its Two Methyl Analogues in α-Melanocyte Stimulating Hormone-Triggered B16/F10 Murine Melanoma Cells

    Science.gov (United States)

    Yoon, Hoon-Seok; Hyun, Chang-Gu; Lee, Nam-Ho; Park, Sung-Soo; Shin, Dong-Bum

    2016-01-01

    Previous research showed that resveratrol (trans-3,4′,5-trihydroxystilbene) and pinostilbene (trans-3-methoxy-4′,5-dihydroxystilbene) were able to inhibit tyrosinase directly; however, anti-melanogenic effects of pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene) and resveratrol trimethyl ether (RTE) have not been compared. To investigate the hypopigmentation effects of pterostilbene and RTE, melanin contents and intracellular tyrosinase activity were determined by western blot analysis. Firstly, pterostilbene showed the inhibitory effects on α-melanocyte stimulating hormone (MSH)-induced melanin synthesis stronger than RTE, resveratrol, and arbutin. Pterostilbene inhibited melanin biosynthesis in a dose-dependent manner in α-MSH-stimulated B16/F10 murine melanoma cells. Specifically, melanin content and intracellular tyrosinase activity were inhibited by 63% and 58%, respectively, in response to treatment with 10 μM of pterostilbene. The results of western blot analysis indicated that pterostilbene induced downregulation of tyrosinase protein expression and suppression of α-MSH-stimulated melan-A protein expression stronger than RTE or resveratrol. Based on these results, our study suggests that pterostilbene can induce hypopigmentation effects more effectively than resveratrol and RTE, and it functions via downregulation of protein expression associated with hyperpigmentation in α-MSH-triggered B16/F10 murine melanoma cells. PMID:27390733

  17. Antiangiogenesis, Loss of Cell Adhesion and Apoptosis Are Involved in the Antitumoral Activity of Proteases from V. cundinamarcensis (C. candamarcensis in Murine Melanoma B16F1

    Directory of Open Access Journals (Sweden)

    Dalton Dittz

    2015-03-01

    Full Text Available The proteolytic enzymes from V. cundinamarcensis latex, (P1G10, display healing activity in animal models following various types of lesions. P1G10 or the purified isoforms act as mitogens on fibroblast and epithelial cells by stimulating angiogenesis and wound healing in gastric and cutaneous ulcers models. Based on evidence that plant proteinases act as antitumorals, we verified this effect on a murine melanoma model. The antitumoral effect analyzed mice survival and tumor development after subcutaneous administration of P1G10 into C57BL/6J mice bearing B16F1 low metastatic melanoma. Possible factors involved in the antitumoral action were assessed, i.e., cytotoxicity, cell adhesion and apoptosis in vitro, haemoglobin (Hb, vascular endothelial growth factor (VEGF, tumor growth factor-β (TGF-β, tumor necrosis factor-α (TNF-α content and N-acetyl-glucosaminidase (NAG activity. We observed that P1G10 inhibited angiogenesis measured by the decline of Hb and VEGF within the tumor, and TGF-β displayed a non-significant increase and TNF-α showed a minor non-significant reduction. On the other hand, there was an increase in NAG activity. In treated B16F1 cells, apoptosis was induced along with decreased cell binding to extracellular matrix components (ECM and anchorage, without impairing viability.

  18. ADHESION-INDUCE PROTEIN TYROSINE PHOSPHORY-LATION IS ASSOCIATED WITH INVASIVE AND METASTATIC POTENTIALS IN B16-BL6 MELANOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    Yan Chunhong; Han Rui

    1998-01-01

    Objective: The interaction of cancer cell with extracellular matrix (ECM) happens as an earlier and specific event in the invasive and metastatic cascade. To explore the key element(s) in cancer metastasis and observe the cell-ECM interaction and its role. Methods:To interrupt the cell-ECM interaction by suppression of adhesion-induced protein tyrosine phosphorylation with protein tyrosine kinase inhibitor genistein in B16-B16mouse melanoma cells. Results: When B16-BL6 cells attached to Matrigel, a solubilized basement membrane preparation from EHS sarcoma, a 125 kDa protein increased its phosphotyrosine content dramatically. In contrast, when the cells were pretreated with 20μM or 30μM genistein for 3 days, it was revealed a less increase in the phosphotyrosine content of this 125 kDa protein inresponse to cell attachment to ECM was revealed with immunoblot analysis. Accompanied by the lower level of adhesion-induced protein tyrosine phosphorylation the genistein-treated cells exhibited a decrease in their capabilities of adhesion to Matrigel and invasion through reconstituted basement membrane. The potentials of and forming lung metastatic nodules were also shown to be decreased dramatically in these genistein-treated cells.Conclusion: It was suggested that protein tyrosine phosphorylation in cell-ECM interaction might be associated with invasive and metastatic potentials in cancer cells.

  19. Melanogenesis stimulation in B16-F10 melanoma cells induces cell cycle alterations, increased ROS levels and a differential expression of proteins as revealed by proteomic analysis

    International Nuclear Information System (INIS)

    Considering that stimulation of melanogenesis may lead to alterations of cellular responses, besides melanin production, our main goal was to study the cellular effects of melanogenesis stimulation of B16-F10 melanoma cells. Our results show increased levels of the reactive oxygen species after 15 h of melanogenesis stimulation. Following 48 h of melanogenesis stimulation, proliferation was inhibited (by induction of cell cycle arrest in the G1 phase) and the expression levels of p21 mRNA were increased. In addition, melanogenesis stimulation did not induce cellular senescence. Proteomic analysis demonstrated the involvement of proteins from other pathways besides those related to the cell cycle, including protein disulfide isomerase A3, heat-shock protein 70, and fructose biphosphate aldolase A (all up-regulated), and lactate dehydrogenase (down-regulated). In RT-qPCR experiments, the levels of pyruvate kinase M2 mRNA dropped, whereas the levels of ATP synthase (beta-F1) mRNA increased. These data indicate that melanogenesis stimulation of B16-F10 cells leads to alterations in metabolism and cell cycle progression that may contribute to an induction of cell quiescence, which may provide a mechanism of resistance against cellular injury promoted by melanin synthesis. -- Highlights: ► Melanogenesis stimulation by L-tyrosine+NH4Cl in B16-F10 melanoma cells increases ROS levels. ► Melanogenesis inhibits cell proliferation, and induced cell cycle arrest in the G1 phase. ► Proteomic analysis showed alterations in proteins of the cell cycle and glucose metabolism. ► RT-qPCR analysis confirmed alterations of metabolic targets after melanogenesis stimulation.

  20. Melanogenesis stimulation in B16-F10 melanoma cells induces cell cycle alterations, increased ROS levels and a differential expression of proteins as revealed by proteomic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Elizabeth S.; Kawahara, Rebeca [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Kadowaki, Marina K. [Universidade Estadual do Oeste do Parana, Cascavel, PR (Brazil); Amstalden, Hudson G.; Noleto, Guilhermina R.; Cadena, Silvia Maria S.C.; Winnischofer, Sheila M.B. [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Martinez, Glaucia R., E-mail: grmartinez@ufpr.br [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil)

    2012-09-10

    Considering that stimulation of melanogenesis may lead to alterations of cellular responses, besides melanin production, our main goal was to study the cellular effects of melanogenesis stimulation of B16-F10 melanoma cells. Our results show increased levels of the reactive oxygen species after 15 h of melanogenesis stimulation. Following 48 h of melanogenesis stimulation, proliferation was inhibited (by induction of cell cycle arrest in the G1 phase) and the expression levels of p21 mRNA were increased. In addition, melanogenesis stimulation did not induce cellular senescence. Proteomic analysis demonstrated the involvement of proteins from other pathways besides those related to the cell cycle, including protein disulfide isomerase A3, heat-shock protein 70, and fructose biphosphate aldolase A (all up-regulated), and lactate dehydrogenase (down-regulated). In RT-qPCR experiments, the levels of pyruvate kinase M2 mRNA dropped, whereas the levels of ATP synthase (beta-F1) mRNA increased. These data indicate that melanogenesis stimulation of B16-F10 cells leads to alterations in metabolism and cell cycle progression that may contribute to an induction of cell quiescence, which may provide a mechanism of resistance against cellular injury promoted by melanin synthesis. -- Highlights: Black-Right-Pointing-Pointer Melanogenesis stimulation by L-tyrosine+NH{sub 4}Cl in B16-F10 melanoma cells increases ROS levels. Black-Right-Pointing-Pointer Melanogenesis inhibits cell proliferation, and induced cell cycle arrest in the G1 phase. Black-Right-Pointing-Pointer Proteomic analysis showed alterations in proteins of the cell cycle and glucose metabolism. Black-Right-Pointing-Pointer RT-qPCR analysis confirmed alterations of metabolic targets after melanogenesis stimulation.

  1. Inhibitory Effect of Dried Pomegranate Concentration Powder on Melanogenesis in B16F10 Melanoma Cells; Involvement of p38 and PKA Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Su Jin Kang

    2015-10-01

    Full Text Available Plants rich in antioxidant substances may be useful for preventing skin aging. Pomegranates, containing flavonoids and other polyphenolic compounds, are widely consumed due to their beneficial properties. We examined the underlying mechanisms of dried pomegranate concentrate powder (PCP on melanin synthesis in B16F10 melanoma cells. The antioxidant effects of PCP were determined by measuring free radical scavenging capacity and transcript levels of antioxidant enzymes. To explore the inhibitory effects of PCP on melanin synthesis, we measured tyrosinase activity and melanin content in α-melanocyte stimulating hormone (α-MSH-stimulated B16F10 cells. In addition, the levels of tyrosinase-related protein-1 (TRP-1, TRP-2, tyrosinase, and microphthalmia-associated transcription factor (MITF expression were determined by Western blotting. Changes in the phosphorylation status of protein kinase A (PKA, cAMP response element-binding protein (CREB, mitogen-activated protein kinases (MAPKs, phosphatidylinositol 3-kinase (PI3K, serine/threonine kinase Akt, and glycogen kinase 3β (GSK3β were also examined. The free radical scavenging activity of PCP increased in a dose-dependent manner. In PCP-treated B16F10 cells, transcript levels of glutathione peroxidase-1 (GPx-1 were increased compared with α-MSH-stimulated cells. In addition, PCP led to the down-regulation of phospho-p38, phospho-PKA, phospho-CREB, phospho-GSK3β, MITF, and TRP-1 compared with α-MSH-stimulated B16F10 cells. We believe this effect may be associated with PCP activity, which leads to the inhibition of melanin production and tyrosinase activity. These results suggest that PCP decreases tyrosinase activity and melanin production via inactivation of the p38 and PKA signaling pathways, and subsequently decreases phosphorylation of CREB, MITF, and melanogenic enzymes. These observations provided new insights on the molecular mechanisms of the skin-whitening property of PCP.

  2. Inhibitory effect of Cucumis sativus on melanin production in melanoma B16 cells by downregulation of tyrosinase expression.

    Science.gov (United States)

    Kai, Hisahiro; Baba, Masaki; Okuyama, Toru

    2008-12-01

    We compared the inhibitory effects on melanogenesis of six plant parts (leaves, stems, roots, whole fruits, calyxes, and fruits without calyxes) of Cucumis sativus. MeOH extracts of leaves and stems inhibited melanin production in B16 cells. These extracts did not affect the activity of mushroom tyrosinase or crude enzyme lysate from B16 cells. However, the extracts decreased tyrosinase expression at the protein level. These results suggest that the depigmenting mechanism of extracts from leaves and stems of C. SATIVUS involves the expression of tyrosinase. Of eight compounds isolated from the leaves, lutein ( 1) (IC (50) = 170.7 microM) and (+)-(1 R,2 S,5 R,6 S)-2,6-di-(4'-hydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane ( 2) (IC (50) = 270.8 microM) were found to suppress melanogenesis. Whereas 1 was found to markedly decrease the expression levels of tyrosinase, 2 only weakly reduced tyrosinase expression. This suggests that 1 is an active component in the leaves of C. sativus and is a potentially useful skin-whitening agent. PMID:19009501

  3. Inhibitory Effects of Adlay Extract on Melanin Production and Cellular Oxygen Stress in B16F10 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Huey-Chun Huang

    2014-09-01

    Full Text Available The aim of this study was to determine the effects of adlay extract on melanin production and the antioxidant characteristics of the extract. The seeds were extracted by the supercritical fluid CO2 extraction (SFE method. The effect of adlay extract on melanin production was evaluated using mushroom tyrosinase activity assay, intracellular tyrosinase activity, antioxidant properties and melanin content. Those assays were performed spectrophotometrically. In addition, the expression of melanogenesis-related proteins was determined by western blotting. The results revealed that the adlay extract suppressed intracellular tyrosinase activity and decreased the amount of melanin in B16F10 cells. The adlay extract decreased the expression of microphthalmia-associated transcription factor (MITF, tyrosinase, tyrosinase related protein-1 (TRP-1 and tyrosinase related protein-2 (TRP-2. The extract also exhibited antioxidant characteristics such as free radical scavenging capacity and reducing power. It effectively decreased intracellular reactive oxygen species (ROS levels in B16F10 cells. We concluded that the adlay extract inhibits melanin production by down-regulation of MITF, tyrosinase, TRP-1 and TRP-2. The antioxidant properties of the extract may also contribute to the inhibition of melanogenesis. The adlay extract can therefore be applied as an inhibitor of melanogenesis and could also act as a natural antioxidant in skin care products.

  4. The leaf extract ofMallotus japonicus and its major active constituent, rutin, suppressed on melanin production in murine B16F1 melanoma

    Institute of Scientific and Technical Information of China (English)

    Junsei Taira; Eito Tsuchida; Masatsugu Uehara; Natsuko Ohhama; Wakana Ohmine; Takayuki Ogi

    2015-01-01

    Objective:To find anti-melanogenesis materials used in whitening cosmetics. Methods: The ethanolic leaf extract ofMallotus japonicus (M. japonicus) having an anti-melanogenesis activity was separated by a sephadexLH-20 chromatography. Each fraction was measured for its tyrosinase inhibitory activity together with its polyphenol content using the Folin–Ciocalteu method. The anti-melanogenesis activity of the active fractions was determined by the melanin content in the murine B16F1 melanoma. The active fractions were put together due to similar constituents, and then separated by high performance liquid chromatography using a C-18 ODS column. The major anti-melanogenesis compound was identified using 1Hand13C-NMR and liquid chromatography-mass spectrometry. Results: The ethanolic leaf extract ofM. japonicus showed an anti-tyrosinase activity with a high polyphenol content, resulting in suppression of melanin production in the B16F1 melanoma. The extract was separated and the active compound was identical as rutin based on the1H,13C-NMR and liquid chromatography-mass spectrometry analysis data. In addition, the rutin treatment with cells reduced the melanin content in a concentration dependent manner without any cell toxicity. The leaf extract ofM. japonicus containing rutin would be useful in whitening cosmetics for protection from UV-light exposure to be limiting the accumulation of melanin in skin. Conclusions: The leaf extract ofM. japonicus and/or rutin isolated from the extract as a key whitening agent would be useful as a whitening cosmetic material for protecting against disorder skin due to melanin accumulation.

  5. Activation of MITF by Argan Oil Leads to the Inhibition of the Tyrosinase and Dopachrome Tautomerase Expressions in B16 Murine Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Myra O. Villareal

    2013-01-01

    Full Text Available Argan (Argania spinosa L. oil has been used for centuries in Morocco as cosmetic oil to maintain a fair complexion and to cure skin pimples and chicken pox pustules scars. Although it is popular, the scientific basis for its effect on the skin has not yet been established. Here, the melanogenesis regulatory effect of argan oil was evaluated using B16 murine melanoma cells. Results of melanin assay using B16 cells treated with different concentrations of argan oil showed a dose-dependent decrease in melanin content. Western blot results showed that the expression levels of tyrosinase (TYR, tyrosinase-related protein 1 (TRP1, and dopachrome tautomerase (DCT proteins were decreased. In addition, there was an increase in the activation of MITF and ERK1/2. Real-time PCR results revealed a downregulation of Tyr, Trp1, Dct, and Mitf mRNA expressions. Argan oil treatment causes MITF phosphorylation which subsequently inhibited the transcription of melanogenic enzymes, TYR and DCT. The inhibitory effect of argan oil on melanin biosynthesis may be attributed to tocopherols as well as the synergistic effect of its components. The results of this study provide the scientific basis for the traditionally established benefits of argan oil and present its therapeutic potential against hyperpigmentation disorders.

  6. Activation of MITF by Argan Oil Leads to the Inhibition of the Tyrosinase and Dopachrome Tautomerase Expressions in B16 Murine Melanoma Cells.

    Science.gov (United States)

    Villareal, Myra O; Kume, Sayuri; Bourhim, Thouria; Bakhtaoui, Fatima Zahra; Kashiwagi, Kenichi; Han, Junkyu; Gadhi, Chemseddoha; Isoda, Hiroko

    2013-01-01

    Argan (Argania spinosa L.) oil has been used for centuries in Morocco as cosmetic oil to maintain a fair complexion and to cure skin pimples and chicken pox pustules scars. Although it is popular, the scientific basis for its effect on the skin has not yet been established. Here, the melanogenesis regulatory effect of argan oil was evaluated using B16 murine melanoma cells. Results of melanin assay using B16 cells treated with different concentrations of argan oil showed a dose-dependent decrease in melanin content. Western blot results showed that the expression levels of tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase (DCT) proteins were decreased. In addition, there was an increase in the activation of MITF and ERK1/2. Real-time PCR results revealed a downregulation of Tyr, Trp1, Dct, and Mitf mRNA expressions. Argan oil treatment causes MITF phosphorylation which subsequently inhibited the transcription of melanogenic enzymes, TYR and DCT. The inhibitory effect of argan oil on melanin biosynthesis may be attributed to tocopherols as well as the synergistic effect of its components. The results of this study provide the scientific basis for the traditionally established benefits of argan oil and present its therapeutic potential against hyperpigmentation disorders. PMID:23935660

  7. VEGF-C Promotes Immune Tolerance in B16 Melanomas and Cross-Presentation of Tumor Antigen by Lymph Node Lymphatics

    Directory of Open Access Journals (Sweden)

    Amanda W. Lund

    2012-03-01

    Full Text Available Tumor expression of the lymphangiogenic factor VEGF-C is correlated with metastasis and poor prognosis, and although VEGF-C enhances transport to the draining lymph node (dLN and antigen exposure to the adaptive immune system, its role in tumor immunity remains unexplored. Here, we demonstrate that VEGF-C promotes immune tolerance in murine melanoma. In B16 F10 melanomas expressing a foreign antigen (OVA, VEGF-C protected tumors against preexisting antitumor immunity and promoted local deletion of OVA-specific CD8+ T cells. Naive OVA-specific CD8+ T cells, transferred into tumor-bearing mice, were dysfunctionally activated and apoptotic. Lymphatic endothelial cells (LECs in dLNs cross-presented OVA, and naive LECs scavenge and cross-present OVA in vitro. Cross-presenting LECs drove the proliferation and apoptosis of OVA-specific CD8+ T cells ex vivo. Our findings introduce a tumor-promoting role for lymphatics in the tumor and dLN and suggest that lymphatic endothelium in the local microenvironment may be a target for immunomodulation.

  8. The Viscum album preparation Isorel inhibits the growth of melanoma B16F10 by influencing the tumour-host relationship.

    Science.gov (United States)

    Zarkovic, N; Zarkovic, K; Grainca, S; Kissel, D; Jurin, M

    1997-04-01

    The aim of this study was to analyse whether Viscum album (mistletoe; Isorel) modulates the tumour-host relationship and whether this might be a basic mechanism of the antitumorous activity of the drug. The effects of a single intraperitoneal injection of the drug (100 mg/kg single 'planta tota' dose) were analysed for mice-bearing melanoma B16F10 growing in the hind limb. Injection of Isorel reduced the size of the tumour and caused abundant tumour necrosis with inflammatory response, oedema and destruction of the malignant tissue. Furthermore, the lymphocytes of saline-treated tumorous mice were not able to respond to the mitogenic lectin concanavalin A in vitro, while those of mistletoe extract-treated mice showed high reactivity too the mitogen, but only if cultured in the medium supplemented with the plasma of the mistletoe extract-treated mice. Moreover, melanoma cells exposed to the mistletoe extract were more sensitive to the cytotoxic activity of the lymphocytes than the control tumour cells, particularly in the presence of the plasma of mistletoe extract-treated mice. The plasma itself, however, did not show any cytotoxic activity. These results indicate that the antitumour activity of the mistletoe drug is due to a modulation of the tumour-host relationship, mediated by direct cytotoxicity of the drug to tumour cells and/or through a potentiation of immune response by certain, as yet unidentified, growth modifying humoral factors of the host. PMID:9179362

  9. Paullinia cupana Mart var. sorbilis, guaraná, reduces cell proliferation and increases apoptosis of B16/F10 melanoma lung metastases in mice

    Directory of Open Access Journals (Sweden)

    H. Fukumasu

    2008-04-01

    Full Text Available We showed that guaraná (Paullinia cupana Mart var. sorbilis had a chemopreventive effect on mouse hepatocarcinogenesis and reduced diethylnitrosamine-induced DNA damage. In the present experiment, we evaluated the effects of guaraná in an experimental metastasis model. Cultured B16/F10 melanoma cells (5 x 10(5 cells/animal were injected into the tail vein of mice on the 7th day of guaraná treatment (2.0 mg P. cupana/g body weight, per gavage and the animals were treated with guaraná daily up to 14 days until euthanasia (total treatment time: 21 days. Lung sections were obtained for morphometric analysis, apoptotic bodies were counted to calculate the apoptotic index and proliferating cell nuclear antigen-positive cells were counted to determine the proliferation index. Guaraná-treated (GUA animals presented a 68.6% reduction in tumor burden area compared to control (CO animals which were not treated with guaraná (CO: 0.84 ± 0.26, N = 6; GUA: 0.27 ± 0.24, N = 6; P = 0.0043, a 57.9% reduction in tumor proliferation index (CO: 23.75 ± 20.54, N = 6; GUA: 9.99 ± 3.93, N = 6; P = 0.026 and a 4.85-fold increase in apoptotic index (CO: 66.95 ± 22.95, N = 6; GUA: 324.37 ± 266.74 AB/mm², N = 6; P = 0.0152. In this mouse model, guaraná treatment decreased proliferation and increased apoptosis of tumor cells, consequently reducing the tumor burden area. We are currently investigating the molecular pathways of the effects of guaraná in cultured melanoma cells, regarding principally the cell cycle inhibitors and cyclins.

  10. Inhibition of honokiol on the proliferation and melanin biosynthesis on B16 melanoma cells in vitro%和厚朴酚对小鼠黑色素瘤B16细胞增殖以及黑色素合成的影响

    Institute of Scientific and Technical Information of China (English)

    喻丽红; 张超; 谭茵

    2012-01-01

    Objective To investigate the inhibition of honokiol on proliferation and melanin biosynthesis in B16 melanoma cells in vitro. Methods B16 cells were cultured in vitro. MTT assay, DAPI and NaOH lysis test were applied for assessment of cell proliferation, cellular morphologic observation and cellular melanin content, respectively. Results B16 cells were treated with honokiol with different concentrations ( 5,10,20,40 and 80 μmol/L ) and durations ( 12,24 and 48 h ). The IC50 of honokiol on proliferation of B16 cells were 23. 4, 13. 1 and 11.4 μmol/L, respectively, with durations of 12,24 and 48 h. Apoptosis of B16 cells were induced with honokiol in DAPI staining. Furthermore, the melanin biosynthesis was inhibited with honokiol with concentration over 20 (xmol/L. Conclusion Honokiol effectively inhibits the proliferation of B16 in dose - and time - depend manners. Apoptotic bodies were observed in B16 cells treated with honokiol. Although melanin biosynthesis is also inhibited by honokiol, this effect is insignificant.%目的 探讨和厚朴酚对小鼠黑色素瘤B16细胞增殖以及细胞内黑色素合成的影响.方法 体外培养小鼠B16细胞,MTT法检测和厚朴酚对B16细胞增殖的影响;DAPI染色法观察和厚朴酚对B16细胞细胞形态的影响;NaOH裂解法检测和厚朴酚对黑色素含量的影响.结果 和厚朴酚浓度为5、10、20、40、80 μmol/L 作用B16细胞,在不同的用药时间12、24和48 h,和厚朴酚对B16细胞增殖的IC50分别为23.4、13.1和11.4 μmol/L;同时和厚朴酚作用B16细胞12 h后,经DAPI染色,B16细胞呈现典型的凋亡形态;另外采用20、40、80 μmol/L的和厚朴酚分别作用B16细胞,B16细胞内黑色素合成量也呈现降低的趋势.结论 和厚朴酚能有效地抑制B16细胞增殖,且其抑制作用具有时间和浓度依赖性;药物作用后的B16细胞呈现凋亡形态并出现凋亡小体;和厚朴酚对B16细胞内黑色素合成也呈现抑制作用但不明显.

  11. A biodistribution study of PEGylated PCL-based nanoparticles in C57BL/6 mice bearing B16/F10 melanoma

    International Nuclear Information System (INIS)

    One of the major drawbacks that limits the clinical application of nanoparticles is the lack of preliminary investigations related to their biocompatibility, biodegradability and biodistribution. In this work, biodegradable PEGylated polymer nanoparticles (NPs) have been synthesized by using macromonomers based on poly(ε-caprolaconte) oligomers. More in detail, NPs have been produced by adopting a surfactant-free semibatch emulsion polymerization process using PEG chains as a stabilizing agent. The NPs were also labeled with rhodamine B covalently bound to the NPs to quantitatively study their biodistribution in vivo. NPs were investigated in both in vitro and in vivo preclinical systems to study their biodistribution in mice bearing B16/F10 melanoma, as well as their biocompatibility and biodegradability. The NP concentration was evaluated in different tissues at several times after intravenous injection. The disappearance of the NPs from the plasma was biphasic, with distribution and elimination half-lives of 30 min and 15 h, respectively. NPs were retained in tumors and in filter organs for a long time, were still detectable after 7 d and maintained a steady concentration in the tumor for 120 h. 48 h after injection, 70 ± 15% of the inoculated NPs were excreted in the feces. The favorable tumor uptake, fast excretion and absence of cytotoxicity foster the further development of produced NPs as drug delivery carriers. (paper)

  12. Penurunan Aktivitas Tirosinase dan Jumlah Melanin oleh Fraksi Etil Asetat Buah Malaka (Phyllantus emblica pada Mouse Melanoma B16 Cell-Line

    Directory of Open Access Journals (Sweden)

    Reti Hindritiani

    2013-06-01

    Full Text Available Melanin accumulation can lead to hyperpigmentation, and if it occurs on the face can cause psychosocial problem. Depigmenting agents derived from plants are increasingly utilized. Agents being developed have to be effective in inhibiting melanin synthesis and should not be toxic to melanocyte. This study aimed was to examine the effect of ethyl acetate fraction from Phyllanthus emblica (P. emblica fruit, also known as malaka fruit, towards melanine synthesis, which was measured from the melanin amount and tyrosinase activity, the key regulatory enzyme in melanin synthesis, spectrophotometrically towards melanocytes of mouse melanoma B16 cell-line. The cytotoxic effect towards melanocytes was measured with 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT assay. This study was conducted on November−December 2009 in Department of Biochemistry and Diabetes Research Centre, Chonbuk National University Medical School, South Korea. The result of this study showed that tyrosinase activity and melanin amount decreased in a dose-dependent manner towards various concentrations of ethyl acetate fraction of P. emblica fruit with inhibition concentration (IC 50=95.63 and 16.90 μg/mL, respectively and lethal dose (LD 50 concentration 106.64 μg/mL. In conclusion, ethyl acetate fraction of P. emblica fruit is a potential depigmenting agent, since it can reduce melanin synthesis by inhibition of tyrosinase activity.

  13. Systematic review of melanoma incidence and prognosis in solid organ transplant recipients

    OpenAIRE

    Dahlke, Erin; Murray, Christian Alexander; Kitchen, Jessica; Chan, An-Wen

    2014-01-01

    Cutaneous melanoma carries the potential for substantial morbidity and mortality in the solid organ transplant population. We systematically reviewed the literature published from January 1995 to January 2012 to determine the overall relative risk and prognosis of melanoma in transplant recipients. Our search identified 7,512 citations. Twelve unique non-overlapping studies reported the population-based incidence of melanoma in an inception cohort of solid organ transplant recipients. Compare...

  14. Antitumor Effects In Vitro and In Vivo and Mechanisms of Protection against Melanoma B16F10-Nex2 Cells By Fastuosain, a Cysteine Proteinase from Bromelia fastuosa1

    OpenAIRE

    Guimarães-Ferreira, Carla A; Rodrigues, Elaine G; Renato A Mortara; Cabral, Hamilton; Fabiana A. Serrano; Ribeiro-dos-Santos, Ricardo; Travassos, Luiz R.

    2007-01-01

    In the present work, the antitumor effect of fastuosain, a cysteine proteinase from Bromelia fastuosa, was investigated. In the intravenous model of lung colonization in C57Bl/6 mice, fastuosain and bromelain injected intraperitoneally were protective, and very few nodules of B16F10-Nex2 melanoma cells were detected. Tumor cells treated with fastuosain showed reduced expression of CD44 and decreased invasion through Matrigel, lost their cytoplasmic extensions and substrate adherence, and beca...

  15. Effects of serum containing Tribulus terrestris on proliferation and melanogenesis in cultured B16 melanoma cells%刺蒺藜血清对小鼠B16黑素瘤细胞增殖及黑素合成的影响

    Institute of Scientific and Technical Information of China (English)

    杨柳; 谢家宝; 洪逊强; 刘利利; 马玲玲

    2011-01-01

    Objective To observe the effects of serum containing Tribulus terrestris on proliferation and melanogenesis in B16 melanoma cells.Methods B16 melanoma cells was cultured in vitro.Serum containing Tribulus terrestris was prepared.MTT and NaOH method were used to detect proliferation and melanogenesis respectively.Results The serum containing Tribulus terrestris increased the amount of melanin at higher concentrations (30g) but acted to the reverse effect at lower concentrations (10g) (P<0.01).Compared with blank control group,The amount of melanin at middle concentrations (20g) had no significant difference (P>0.05).Conclusions the effects of serum containing Tribulus terrestris on proliferation and melanogenesis in B16 melanoma cells correlated with the concentration of Tribulus terrestris.lt presented a two-way regulation on proliferation and melanogenesis in cultured B16 melanoma cells.%目的:探讨刺蒺藜血清对黑素瘤细胞增殖及黑素合成的影响.方法:体外培养小鼠B16黑素瘤细胞,制备大鼠含药血清,分别采用四甲基偶氮唑蓝比色法(MTT法)和NaOH裂解法检测细胞增殖及黑素含量.结果:刺蒺藜对黑素细胞增殖及黑素含量具有低剂量(10g)抑制、高剂量(30g)促进作用(P<0.01),中剂量(20g)对细胞增殖及黑素含量的影响倾向于促进作用,但与空白对照组比较无统计学意义.结论:刺蒺藜对黑素细胞增殖及黑素含量的影响与剂量有关,具有低浓度抑制,高浓度激活的双向调节作用.

  16. In vitro and in vivo antitumor efficacy of CLA-PTX on B16-F10 melanoma cells%CLA-PTX对黑色素瘤B16-F10的体内外抗肿瘤作用

    Institute of Scientific and Technical Information of China (English)

    李捷思; 杨科; 柯曦宇; 杜若; 张烜; 张强

    2014-01-01

    本研究旨在探索CLA-PTX对黑色素瘤B16-F10细胞的体内外抗肿瘤作用.选择鼠源B16-F10细胞系作为研究模型.研究CLA-PTX体外细胞毒,细胞凋亡,细胞周期作用,以及CLA-PTX体外细胞摄取作用.用荷瘤C57BL6/N小鼠研究CLA-PTX的体内抗肿瘤作用.体外细胞毒研究结果表明:CLA-PTX的ICso为(4.25±0.43) μM,优于紫杉醇(6.70±0.80) μM(P<0.01).与空白组和紫杉醇组相比,CLA-PTX可使细胞总凋亡比例增加(P<0.01).与空白对照组相比,CLA-PTX将细胞周期阻滞于S期,而紫杉醇则使细胞在G2-M期蓄积.CLA-PTX的细胞摄取量显著高于紫杉醇(P<0.01).体内抗肿瘤药效显示,CLA-PTX抗肿瘤活性显著高于空白对照组和紫杉醇组(P<0.01或P<0.05).上述结果表明,CLA-PTX对B16-F10细胞有显著体内外抗肿瘤作用.

  17. Platelet-derived growth factor receptor-β, carrying the activating mutation D849N, accelerates the establishment of B16 melanoma

    International Nuclear Information System (INIS)

    Platelet-derived growth factor (PDGF)-BB and PDGF receptor (PDGFR)-β are mainly expressed in the developing vasculature, where PDGF-BB is produced by endothelial cells and PDGFR-β is expressed by mural cells, including pericytes. PDGF-BB is produced by most types of solid tumors, and PDGF receptor signaling participates in various processes, including autocrine stimulation of tumor cell growth, recruitment of tumor stroma fibroblasts, and stimulation of tumor angiogenesis. Furthermore, PDGF-BB-producing tumors are characterized by increased pericyte abundance and accelerated tumor growth. Thus, there is a growing interest in the development of tumor treatment strategies by blocking PDGF/PDGFR function. We have recently generated a mouse model carrying an activated PDGFR-β by replacing the highly conserved aspartic acid residue (D) 849 in the activating loop with asparagine (N). This allowed us to investigate, in an orthotopic tumor model, the role of increased stromal PDGFR-β signaling in tumor-stroma interactions. B16 melanoma cells lacking PDGFR-β expression and either mock-transfected or engineered to express PDGF-BB, were injected alone or in combination with matrigel into mice carrying the activated PDGFR-β (D849N) and into wild type mice. The tumor growth rate was followed and the vessel status of tumors, i.e. total vessel area/tumor, average vessel surface and pericyte density of vessels, was analyzed after resection. Tumors grown in mice carrying an activated PDGFR-β were established earlier than those in wild-type mice. In this early phase, the total vessel area and the average vessel surface were higher in tumors grown in mice carrying the activated PDGFR-β (D849N) compared to wild-type mice, whereas we did not find a significant difference in the number of tumor vessels and the pericyte abundance around tumor vessels between wild type and mutant mice. At later phases of tumor progression, no significant difference in tumor growth rate was

  18. Platelet-derived growth factor receptor-β, carrying the activating mutation D849N, accelerates the establishment of B16 melanoma

    Directory of Open Access Journals (Sweden)

    Suzuki Shioto

    2007-12-01

    Full Text Available Abstract Background Platelet-derived growth factor (PDGF-BB and PDGF receptor (PDGFR-β are mainly expressed in the developing vasculature, where PDGF-BB is produced by endothelial cells and PDGFR-β is expressed by mural cells, including pericytes. PDGF-BB is produced by most types of solid tumors, and PDGF receptor signaling participates in various processes, including autocrine stimulation of tumor cell growth, recruitment of tumor stroma fibroblasts, and stimulation of tumor angiogenesis. Furthermore, PDGF-BB-producing tumors are characterized by increased pericyte abundance and accelerated tumor growth. Thus, there is a growing interest in the development of tumor treatment strategies by blocking PDGF/PDGFR function. We have recently generated a mouse model carrying an activated PDGFR-β by replacing the highly conserved aspartic acid residue (D 849 in the activating loop with asparagine (N. This allowed us to investigate, in an orthotopic tumor model, the role of increased stromal PDGFR-β signaling in tumor-stroma interactions. Methods B16 melanoma cells lacking PDGFR-β expression and either mock-transfected or engineered to express PDGF-BB, were injected alone or in combination with matrigel into mice carrying the activated PDGFR-β (D849N and into wild type mice. The tumor growth rate was followed and the vessel status of tumors, i.e. total vessel area/tumor, average vessel surface and pericyte density of vessels, was analyzed after resection. Results Tumors grown in mice carrying an activated PDGFR-β were established earlier than those in wild-type mice. In this early phase, the total vessel area and the average vessel surface were higher in tumors grown in mice carrying the activated PDGFR-β (D849N compared to wild-type mice, whereas we did not find a significant difference in the number of tumor vessels and the pericyte abundance around tumor vessels between wild type and mutant mice. At later phases of tumor progression, no

  19. Anti-cancer Effects of CME-1, a Novel Polysaccharide, Purified from the Mycelia of Cordyceps sinensis against B16-F10 Melanoma Cells

    OpenAIRE

    Thanasekaran Jayakumar; Chong-Chi Chiu; Shwu-Huey Wang; Duen-Suey Chou; Yung-Kai Huang; Joen-Rong Sheu

    2014-01-01

    Background: Matrix metalloproteinases (MMPs) play important roles in the invasion and migration of cancer cells. In melanoma, several signaling pathways are constitutively activated. Among these, the mitogen-activated protein kinase (MAPKs) signaling pathways are activated through multiple signal transduction molecules and appear to play major roles in melanoma progression. Therefore, the inhibition of MAPK signaling might be a crucial role for the treatment of melanoma cancer. Aims: We ex...

  20. Irradiated survival effect of melanoma B16 cells at different penetration depths of intermediate energy heavy-ion beams%中能碳离子束对不同贯穿深度上黑色素瘤B16细胞的辐照存活效应

    Institute of Scientific and Technical Information of China (English)

    李强; 周光明; 王菊芳; 李文建; 温小琼; 党秉荣; 颉红梅; 卫增泉

    2001-01-01

    Survival fractions of melanoma B16 cells at different penetrationdepths exposed to 49.30MeV/u 12C ion beam and modulated 74.55MeV/u 12C ion beam with a ridge filter to form a spread-out Bragg peak (SOBP) were measured. The results show the survival response of B16 cells as the biological endpoint to heavy ions increases synchronously with the deposited energy along the beam traversal, that is, the survival fraction near or at the Bragg peak or SOBP is far lower than that at the beam's entrance or exit channel. Comparisons of the experimental data with calculated survival fractions at different depths predicted by the linear-quadratic survival model combined with dose-averaged LET display a good agreement within the experimental errors. It is prompted that the linear-quadratic model combined with dose-averaged LET possibly is a valid way to calculate the survival effect of B16 cells along the beam penetration under the exposure of the intermediate energy heavy-ion beam.%测量了49.30MeV/u及经脊形过滤器展宽的Bragg峰的74.55MeV/u12C离子束在不同贯穿深度上辐射后黑色素瘤B16细胞的存活率。结果显示,以存活为终点的B16细胞生物学效应与碳离子束能量沉积同步增大,即Bragg或展宽的Bragg峰区内细胞存活率远低于离子束入射或出射通道处的细胞存活率。通过实验测量与剂量平均LET结合的线性平方模型理论计算存活曲线的比较,发现在实验测量误差范围内两者符合较好。提示:剂量平均LET结合线性平方模型可能是预测中能重离子束贯穿深度上B16细胞存活效应的一种有效的方法。

  1. Ardisia crenata extract stimulates melanogenesis in B16F10 melanoma cells through inhibiting ERK1/2 and Akt activation.

    Science.gov (United States)

    Yao, Cheng; Jin, Cheng Long; Oh, Jang-Hee; Oh, Inn Gyung; Park, Chi-Hyun; Chung, Jin Ho

    2015-01-01

    Melanin protects the skin against ultraviolet radiation by scattering incoming light and absorbing diverse free radicals. Agents that increase melanin synthesis in melanocytes may reduce the risk of photodamage and skin cancer. The present study investigated the effect of a methanol extract of Ardisia crenata (AC) on melanogenesis in B16F10 cells. Treatment of cultured B16F10 cells with AC extract (10, 20 and 40 µg/ml) stimulated an increase in melanin levels in a concentration-dependent manner, without cytotoxicity. Tyrosinase is key in the regulation of melanin production, thus the effect of AC extract on tyrosinase activity and protein expression was analyzed. AC extract was observed to significantly increase tyrosinase activity and protein expression in B16F10 cells. Furthermore, AC extract was found to markedly increase the protein expression of microphthalmia-associated transcription factor, which is an important transcription factor involved in tyrosinase gene expression. In addition, AC extract (40 µg/ml) was observed to suppress the activation of extracellular signal-regulated kinase (ERK) and Akt, which negatively regulate melanin synthesis in B16F10 cells. In conclusion, to the best of our knowledge, the present study is the first to show that a methanol extract of AC stimulates melanogenesis by increasing tyrosinase expression via the inhibition of ERK and Akt. Thus, methanol extract of AC may be a potential treatment for hypopigmentation diseases and may be a candidate for skin-tanning cosmetic products. PMID:25333888

  2. 转染人核糖核酸酶抑制因子基因对B16黑色瘤细胞及肿瘤转移的影响%Effects of Transfection of Human Ribonuclease Inhibitor Gene on B16 Melanoma Cells and Tumor Metastasis

    Institute of Scientific and Technical Information of China (English)

    陈俊霞; 田余祥; 傅攀峰; 夏俊; 阎平; 崔秀云

    2004-01-01

    Human ribonuclease inhibitor (RI) is an acidic cytoplasmic glycoprotein with molecular mass of 50 ku. RI can inhibit the activity of ribonuclease A ( RNase A). Angiogenin (Ang) is a member of RNase A superfamily. RI also can inhibit Ang activities by tight combination. Angiogenesis is an essential condition for the development of tumors and their metastatic dissemination. So anti-angiogenesis will be an efficient method in the inhibition of the growth and metastasis of tumor. The experiment demonstrated that RI might effectively block the angiogenesis that was induced by angiogenin. RI is constructed almost entirely of leucine-rich repeats that might involve in other unclear biological effect. In order to understand further the potential function of RI and investigate the role of RI in invasion and metastasis. The study established a transfection of human RI cDNA into B16 melanoma cells by the retroviral packaging cell line PA317 carrying the pLNCX-RI in vitro. Transfected B16 cells by PA317 carrying the pLNCX and untransfected B16 cells were used as control. The B16pLNCX-RI cell line with a stably high expression of RI was identified by PCR, RT-PCR, Western blot and immunofluorescence assay respectively. The results showed that the transfected RI gene might significantly inhibit cell proliferation, migration, and enhance cell adhesion, as well as, make morphological changes in vitro. Cell doubling time were (24.98 ±0.16) h, (25.62 ±0.28) h, (32.64 + 1.11) h in B16 cells, B16 pLNCX and B16 pLNCX-RI cells respectively. Cell adhesion rate was significantly increased by 19. 5% and 17. 8% as well as cell migration was reduced by 60% and 61.4% in B16 pLNCX-RI cells compared with pLNCX B16 cells and B16 cells respectively. B16 pLNCX-RI cells became flatter, less nucleoli, less division phases and weaker alkalophilic quality of cytoplasm compared with control groups, which should imply that cell proliferation viability was decreased and malignant phenotype was improved

  3. Regression of subcutaneous B16 melanoma tumors after intratumoral delivery of an IL-15-expressing plasmid followed by in vivo electroporation

    OpenAIRE

    Ugen, KE; Kutzler, MA; Marrero, B; Westover, J; Coppola, D; Weiner, DB; Heller, R.

    2006-01-01

    In vivo electroporation has been used to efficiently deliver drugs and ‘therapeutic’ genes to tumors, including melanoma lesions. This study reports on the effect of intratumoral delivery of an optimized DNA plasmid expressing interleukin-15 (pIL-15) on established murine melanoma tumors. IL-15 has been demonstrated to have a pivotal role in the function of memory CD8+ T cells and natural killer cells, which are critical for tumor immunosurveillance. In this study, C57BL/6 mice were injected ...

  4. Bio-efficacy of Tea Extract on Mouse B16 Melanoma Cell in Vitro and Its Mechanism%茶叶提取物对B16小鼠黑色素瘤细胞的生物学效应及机理研究

    Institute of Scientific and Technical Information of China (English)

    陈贞纯; 贾玲燕; 毛祖法; 金恩惠; 王广伟; 屠幼英

    2014-01-01

    研究了茶叶提取物对体外培养的 B16小鼠黑色素瘤细胞的生物学效应,并对其机理进行初步探讨。分别用茶黄素单体(TF1)、EGCG、纯度为40%的茶黄素(TF40)处理细胞,然后观察细胞形态,并以溴化二苯四偶氮法(MTT 法)测定受试物对黑色素细胞活力的影响,以左旋多巴为底物测定细胞内酪氨酸酶活性,采用比色法测定细胞中的黑色素含量。实验结果表明,各化合物对B16黑色素瘤细胞形态有不同程度的影响,对细胞活性、酪氨酸酶浓度和黑色素合成量有浓度依赖性抑制作用。这3种茶提取物能通过多种途径抑制黑色素合成,从而达到美白的效果,且茶叶提取物的效果优于Vc。%The Bio-efficacy and mechanism of tea extract on mouse B16 melanoma cell in vitro were studied in this paper. Cells were treated with different concentration of TF1, EGCG and TF40, then the cell morphology was observed. The tyrosinase activity was determined by MTT method. The synthesis of melanin was determined using DOPA as substrate, and proliferation rate of B16 cells was determined by colorimetry, then analyzing the effects of drugs to these indexes. The results showed that the cell morphology was changed by the treatment of drugs. The tyrosinase activity, the synthesis of melanin and proliferation rate of B16 cells were all negatively related to the drugs concentration. Tea extracts and Vc can cause the inhibition of the synthesis of melanin, and result ed to white skin. The whiting effect of tea extracts is better than that of Vc.

  5. 6种中药组方对小鼠B16黑素瘤细胞增殖和黑素生成的影响%The Effect of Six Kinds of Traditional Chinese Herbal Composing Prescriptions on Cell Proliferation and Melanogenesis in Cultured B16 Melanoma Cells

    Institute of Scientific and Technical Information of China (English)

    张建; 巫玮; 万玉华; 张榕文; 刘丹丹; 麻睿; 顾为望

    2011-01-01

    目的 研究6种中药组方水提物、醇提物对小鼠B16黑素瘤细胞增殖及黑素生成的影响.方法 以MTF法测定各组方对B16细胞的增殖活性:NaOH裂解法测定各组方对B16细胞的黑素生成量.结果 组方1、2、3水提物和组方2、4、6醇提物具有明显促细胞增殖作用(P>0.05);水提物中细胞增殖率最高的为组方2(0.625 mg/ml),增殖率为22.60%;醇提物中细胞增殖率最高的为组方4(0.078 mg/ml),增殖率为11.60%.组方1、2、4、5、6水提物和6种组方醇提物均具有促进黑色素生成的作用(P<0.05).水提物中黑素增率最高的为组方1(0.313 mg/ml),增率为75.38%;醇提物中黑素生成增率最高的为组方1(1.25 mg/ml),增率为88.01%.结论 各组方对鼠黑素瘤B16细胞增殖及黑素生成均有一定的促进作用,但其作用强度与组方的组成密切相关.%Objective To study the effects of six ethanol extracts and aqueous extracts from traditional Chinese herbal composing prescriptions on the cell proliferation and melanogenesis in cultured B 16 melanoma cells. Methods The cell proliferation were measured by MTT method, and NaOH assay was to determine melanin synthesis. Results The aqueous extracts of composition 1,2,3 and alcohol extracts of composition 2,4,6 had significantly promoted cell proliferation (P<0.05); aqueous extract with the highest rate of cell proliferation was composing prescription 2 (0.625 mg/ml), the proliferation rate was 22.60%; ethanol extract with the highest rate of cell proliferation was composition 4 (0.078 mg/ml),the proliferation rate was 11.60%. The aqueous extract of composing prescriptions 1,2,4,5,6 and alcohol extracts of the six kinds of composing prescriptions promoted obviously the synthesis of melanin (P<0.05).Aqueous extract with the highest rate of melanin synthesis was composing prescription 1 (0.313 mg/ml),the growth rate is 75.38%; alcohol extract with the highest rate of melanin synthesis was composing

  6. Accumulation of cytolytic CD8{sup +} T cells in B16-melanoma and proliferation of mature T cells in TIS21-knockout mice after T cell receptor stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Min Sook [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of); Woo, Min-Yeong [Department of Microbiology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of); Department of Biomedical Sciences, The Graduate School, Ajou University (Korea, Republic of); Kwon, Daeho [Department of Microbiology, Kwandong University College of Medicine, Gangneung, Gangwon-do 210-701 (Korea, Republic of); Hong, Allen E. [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of); Song, Kye Yong [Department of Pathology, Chung-Ang University College of Medicine, Dongjak-gu, Seoul 156-756 (Korea, Republic of); Park, Sun [Department of Microbiology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of); Lim, In Kyoung [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, 164, World cul-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-380 (Korea, Republic of)

    2014-10-01

    In vivo and in vitro effects of TIS21 gene on the mature T cell activation and antitumor activities were explored by employing MO5 melanoma orthograft and splenocytes isolated from the TIS21-knockout (KO) mice. Proliferation and survival of mature T cells were significantly increased in the KO than the wild type (WT) cells, indicating that TIS21 inhibits the rate of mature T cell proliferation and its survival. In MO5 melanoma orthograft model, the KO mice recruited much more CD8{sup +} T cells into the tumors at around day 14 after tumor cell injection along with reduced tumor volumes compared with the WT. The increased frequency of granzyme B{sup +} CD8{sup +} T cells in splenocytes of the KO mice compared with the WT may account for antitumor-immunity of TIS21 gene in the melanoma orthograft. In contrast, reduced frequencies of CD107a{sup +} CD8{sup +} T cells in the splenocytes of KO mice may affect the loss of CD8{sup +} T cell infiltration in the orthograft at around day 19. These results indicate that TIS21 exhibits antiproliferative and proapoptotic effects in mature T cells, and differentially affects the frequencies of granzyme B{sup +} CD8{sup +} T-cells and CD107a{sup +} CD8{sup +} T-cells, thus transiently regulating in vivo anti-tumor immunity. - Highlights: • Constitutive expression of TIS21 in splenocytes and upregulation by TCR stimulation. • Proliferation of mature T-cells in spleen of TIS21KO mice after TCR stimulation. • Inhibition of cell death in mature T-cells of TIS21KO mice compared with the wild type. • Inhibition of melanoma growth in TIS21KO mice and CD8{sup +} T cell infiltration in tumor. • Reduction of CD 107{sup +}CD8{sup +} T cells, but increased granzyme B{sup +} CD8{sup +} T cells in TIS21KO mice.

  7. Accumulation of cytolytic CD8+ T cells in B16-melanoma and proliferation of mature T cells in TIS21-knockout mice after T cell receptor stimulation

    International Nuclear Information System (INIS)

    In vivo and in vitro effects of TIS21 gene on the mature T cell activation and antitumor activities were explored by employing MO5 melanoma orthograft and splenocytes isolated from the TIS21-knockout (KO) mice. Proliferation and survival of mature T cells were significantly increased in the KO than the wild type (WT) cells, indicating that TIS21 inhibits the rate of mature T cell proliferation and its survival. In MO5 melanoma orthograft model, the KO mice recruited much more CD8+ T cells into the tumors at around day 14 after tumor cell injection along with reduced tumor volumes compared with the WT. The increased frequency of granzyme B+ CD8+ T cells in splenocytes of the KO mice compared with the WT may account for antitumor-immunity of TIS21 gene in the melanoma orthograft. In contrast, reduced frequencies of CD107a+ CD8+ T cells in the splenocytes of KO mice may affect the loss of CD8+ T cell infiltration in the orthograft at around day 19. These results indicate that TIS21 exhibits antiproliferative and proapoptotic effects in mature T cells, and differentially affects the frequencies of granzyme B+ CD8+ T-cells and CD107a+ CD8+ T-cells, thus transiently regulating in vivo anti-tumor immunity. - Highlights: • Constitutive expression of TIS21 in splenocytes and upregulation by TCR stimulation. • Proliferation of mature T-cells in spleen of TIS21KO mice after TCR stimulation. • Inhibition of cell death in mature T-cells of TIS21KO mice compared with the wild type. • Inhibition of melanoma growth in TIS21KO mice and CD8+ T cell infiltration in tumor. • Reduction of CD 107+CD8+ T cells, but increased granzyme B+ CD8+ T cells in TIS21KO mice

  8. Direct visualization of changes of lymphatic function and drainage pathways in lymph node metastasis of B16F10 melanoma using near-infrared fluorescence imaging

    OpenAIRE

    Kwon, Sunkuk; Agollah, Germaine D.; Wu, Grace; Chan, Wenyaw; Sevick-Muraca, Eva M

    2013-01-01

    The lymphatic system provides an initial route for cancer cell dissemination in many cancers including melanoma. However, it is largely unknown how the lymphatic system changes during tumor progression due in part to the lack of imaging techniques currently available. In this study, we non-invasively imaged changes of lymphatic function and drainage patterns using near-infrared fluorescence (NIRF) imaging. Dynamic NIRF imaging following intradermal injection of indocyanine green (ICG) was con...

  9. Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    O-(2-[18F]fluoroethyl) -L-tyrosine([18F]FET) ,a fluorine-18 labeled analogue of tyrosine,has been syn-thesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is com-pleted within 50 min. The radiochemical yield is about 40%(no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [18F]FET shows rapid,high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle(T/M) and tumor-to-blood(T/B) of [18F]FET are similar to those of [18F]FDG,but the ratios of tumor-to-brain(T/Br) are 2-3 times higher than that of [18F]FDG. Autoradiography of [18F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET.

  10. Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

    Institute of Scientific and Technical Information of China (English)

    WANG MingWei; YIN DuanZhi; LI ShiQiang; WANG YongXian

    2007-01-01

    O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), a fluorine-18 labeled analogue of tyrosine, has been synthesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is completed within 50 min. The radiochemical yield is about 40% (no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [18F]FET shows rapid, high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle (T/M) and tumor-to-blood (T/B) of [18F]FET are similar to those of [18F]FDG, but the ratios of tumor-to-brain (T/Br)are 2-3 times higher than that of [18F]FDG. Autoradiography of [18F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET.

  11. Cross-talk between 5-hydroxytryptamine and substance P in the melanogensis and apoptosis of B16F10 melanoma cells.

    Science.gov (United States)

    Zhou, Jia; Geng, Kun-kun; Ping, Feng-feng; Gao, Yue-ying; Liu, Lei; Feng, Bai-nian

    2016-03-15

    Skin pigmentation is a complex process controlled by many different factors. Substance P (SP) regulates many biological functions, including melanogenesis and stress. Our previous study indicated that regulation of SP on melanocyte function was mediated by neurokinin 1 receptor (NK1 receptor). Substantial evidence has accumulated that psychological stress can be associated with skin pigmentation, so that the impact of 5-hydroxytryptamine (5-HT), one of the important factors participating in stress process, on melanogenesis has also been concerned. It has been reported that 5-HT induces melanin synthesis via 5-HT2A receptor. Furthermore, 5-HT2A receptor and NK1 receptor are G-protein coupled receptors (GPCRs) and both expressed on melanocyte, the present study was designed to investigate whether SP has influence on the adjustment function of 5-HT. Our data demonstrated that, SP inhibited 5-HT2A receptor expression to neutralize the pro-melanogenesis effect of 5-HT on B16F10 cells. The up-regulation of NK1 receptor expression was simultaneous with the down-regulation of 5-HT2A receptor treated by SP. This inhibition of 5-HT2A receptor expression by SP could be reversed by NK1 receptor antagonist Spantide I. Our studies indicated that SP could directly induce B16F10 cells apoptosis in vitro. 5-HT and 5-HT2A receptor agonist could mitigate this apoptotic effect of SP. It is the strong evidence of possible cross-talk between GPCRs and giving enlightenments when screening desirable drugs for target receptors. PMID:26872989

  12. Melanoma

    Science.gov (United States)

    Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma ...

  13. 10-Hydroxycamptothecin aerosol treatment inhibits lung metastases in B16F10 melanoma mice models%雾化吸入羟基喜树碱对小鼠B16黑色素瘤实验性肺转移的影响

    Institute of Scientific and Technical Information of China (English)

    张超; 胡巍; 方芸

    2011-01-01

    Objective: To estimate the effect of 10-hydroxycamptothecin (HCPT) to the melanoma lung metastasis mice models and the feasibility of aerosol delivery treatment for lung cancer therapy.Method: BI6FI0 melanoma lung metastasis mice models were made, and nodules number, inhibition rate, tumor area, mean nodules diameter and so on were investigated after the aerosol delivery treatment.Spleen index and thymus index were culculatad at the end of the experiments.The change of body weight, physiological state and the lung tumor tissue in pathological histology were inspeated.Result: The total number of tumor lesions, weight of lungs and the area of lung metastasis of aerosol treatment group had significant difference comparing with normal group and control group.Mean nodules diameter had no significant difference comparing with control group.The spleen index of aerosol treatment group was decreased and thymus index was significantly decreased comparing with normal group and control group.During the treatment there are no obvious changes in physiological state.The lung cancer tissue of aerosol delivery treatment group was recovered in pathological histology.Conclusion: The results suggested that aerosol delivery of HCPT demonstrated powerful antitumor activity and was useful for melanoma lung metastasis by aerosol delivery treatment.%目的:通过雾化10-羟基喜树碱(HCPT)用于治疗B16黑色素瘤肺转移癌小鼠,考察雾化吸入HCPT治疗肺癌的可行性以及疗效.方法:制作B16黑色素瘤肺转移癌小鼠模型,不同剂量雾化给药考察肺转移结节数、肺湿重、肺癌面积、平均直径等参数,计算脾脏指数和胸腺指数,并观察动物的生理生存状况,对肺癌组织进行病理组织学检查.结果:雾化给药组肺癌转移结节数、肺湿重、肺癌面积等参数明显少于模型组,直径相关参数未发生统计学差异;雾化给药组脾脏指数有所减小,胸腺指数较模型组和正常组有显著性差

  14. Natural CD8+25+ regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma

    International Nuclear Information System (INIS)

    Highlights: •CD8+25+ regulatory T cells secrete tolerogenic exosomes. •CD8+25+ regulatory T cell-derived exosomes exhibit immunosuppressive effect. •CD8+25+ regulatory T cell-derived exosomes inhibit antitumor immunity. -- Abstract: Natural CD4+25+ and CD8+25+ regulatory T (Tr) cells have been shown to inhibit autoimmune diseases. Immune cells secrete exosomes (EXOs), which are crucial for immune regulation. However, immunomodulatory effect of natural Tr cell-secreted EXOs is unknown. In this study, we purified natural CD8+25+ Tr cells from C57BL/6 mouse naive CD8+ T cells, and in vitro amplified them with CD3/CD28 beads. EXOs (EXOTr) were purified from Tr cell’s culture supernatants by differential ultracentrifugation and analyzed by electron microscopy, Western blot and flow cytometry. Our data showed that EXOTr had a “saucer” or round shape with 50–100 nm in diameter, contained EXO-associated markers LAMP-1 and CD9, and expressed natural Tr cell markers CD25 and GITR. To assess immunomodulatory effect, we i.v. immunized C57BL/6 mice with ovalbumin (OVA)-pulsed DCs (DCOVA) plus Tr cells or EXOTr, and then assessed OVA-specific CD8+ T cell responses using PE-H-2Kb/OVA tetramer and FITC-anti-CD8 antibody staining by flow cytometry and antitumor immunity in immunized mice with challenge of OVA-expressing BL6–10OVA melanoma cells. We demonstrated that DCOVA-stimulated CD8+ T cell responses and protective antitumor immunity significantly dropped from 2.52% to 1.08% and 1.81% (p OVA (p Tr, respectively. Our results indicate that natural CD8+25+ Tr cell-released EXOs, alike CD8+25+ Tr cells, can inhibit CD8+ T cell responses and antitumor immunity. Therefore, EXOs derived from natural CD4+25+ and CD8+25+ Tr cells may become an alternative for immunotherapy of autoimmune diseases

  15. Natural CD8{sup +}25{sup +} regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Yufeng; Zhang, Xueshu; Zhao, Tuo; Li, Wei; Xiang, Jim, E-mail: jim.xiang@saskcancer.ca

    2013-08-16

    Highlights: •CD8{sup +}25{sup +} regulatory T cells secrete tolerogenic exosomes. •CD8{sup +}25{sup +} regulatory T cell-derived exosomes exhibit immunosuppressive effect. •CD8{sup +}25{sup +} regulatory T cell-derived exosomes inhibit antitumor immunity. -- Abstract: Natural CD4{sup +}25{sup +} and CD8{sup +}25{sup +} regulatory T (Tr) cells have been shown to inhibit autoimmune diseases. Immune cells secrete exosomes (EXOs), which are crucial for immune regulation. However, immunomodulatory effect of natural Tr cell-secreted EXOs is unknown. In this study, we purified natural CD8{sup +}25{sup +} Tr cells from C57BL/6 mouse naive CD8{sup +} T cells, and in vitro amplified them with CD3/CD28 beads. EXOs (EXO{sub Tr}) were purified from Tr cell’s culture supernatants by differential ultracentrifugation and analyzed by electron microscopy, Western blot and flow cytometry. Our data showed that EXO{sub Tr} had a “saucer” or round shape with 50–100 nm in diameter, contained EXO-associated markers LAMP-1 and CD9, and expressed natural Tr cell markers CD25 and GITR. To assess immunomodulatory effect, we i.v. immunized C57BL/6 mice with ovalbumin (OVA)-pulsed DCs (DC{sub OVA}) plus Tr cells or EXO{sub Tr}, and then assessed OVA-specific CD8{sup +} T cell responses using PE-H-2K{sup b}/OVA tetramer and FITC-anti-CD8 antibody staining by flow cytometry and antitumor immunity in immunized mice with challenge of OVA-expressing BL6–10{sub OVA} melanoma cells. We demonstrated that DC{sub OVA}-stimulated CD8{sup +} T cell responses and protective antitumor immunity significantly dropped from 2.52% to 1.08% and 1.81% (p < 0.05), and from 8/8 to 2/8 and 5/8 mice DC{sub OVA} (p < 0.05) in immunized mice with co-injection of Tr cells and EXO{sub Tr}, respectively. Our results indicate that natural CD8{sup +}25{sup +} Tr cell-released EXOs, alike CD8{sup +}25{sup +} Tr cells, can inhibit CD8{sup +} T cell responses and antitumor immunity. Therefore, EXOs derived from

  16. New Sesquiterpene Lactone Dimer, Uvedafolin, Extracted from Eight Yacon Leaf Varieties (Smallanthus sonchifolius): Cytotoxicity in HeLa, HL-60, and Murine B16-F10 Melanoma Cell Lines.

    Science.gov (United States)

    Kitai, Yurika; Hayashi, Kana; Otsuka, Moe; Nishiwaki, Hisashi; Senoo, Tatsuya; Ishii, Tomohiko; Sakane, Genta; Sugiura, Makoto; Tamura, Hirotoshi

    2015-12-23

    Uvedafolin, 1, a new sesquiterpene lactone dimer, was isolated from the leaves of Smallanthus sonchifolius with five related compounds, 2-6, and their cytotoxicity was assessed against three tumor cell lines (HeLa, HL-60, B16-F10 melanoma). The stereostructure of 1 was newly elucidated by ESI-TOF-MS, 1D/2D NMR, and single-crystal X-ray diffraction. Dimers 1 and 2 had the most effective IC50 values, 0.2-1.9 μM, against the three tumor cell lines when compared with monomers 3-6 (IC50 values 0.7-9.9 μM) and etoposide (IC50 values 0.8-114 μM). The ester linkages of two sets of monomers, uvedalin, 5, and sonchifolin, 6, for 1, and enhydrin, 4, and sonchifolin, 6, for 2, as well as the acetyl group at the C-9 position, were essential for the high cytotoxicity. Dimers 1 and 2 would have potential as anticancer agents. PMID:26576855

  17. Effects of Supernatant of CLEC2B Gene Overexpression in Jurkat Cells on the B16 Melanoma cell%CLEC2B基因过表达的Jurkat细胞培养上清液对黑素瘤细胞B16的影响

    Institute of Scientific and Technical Information of China (English)

    张峻岭; 徐士福; 柳君如; 程琳; ZHOU Youwen

    2012-01-01

    目的 将CLEC2B基因过表达的Jurkat细胞培养上清液作用于黑素瘤细胞,观察其上清液对黑素瘤细胞增殖、酪氨酸酶活性、黑素合成的影响,探讨CLEC2B基因在白癜风发病中的作用.方法 培养人淋巴瘤细胞Jurkat细胞和小鼠黑素瘤细胞B16,采用脂质体介导的方法瞬时转染CLEC2B重组质粒入Jurkat细胞,半定量RT-PCR法鉴定CLEC2B基因过表达;将其细胞培养上清液作用于黑素瘤细胞48h后,MTT法检测黑素瘤细胞的增殖情况,多巴氧化法检测酪氨酸酶活性,氢氧化钠裂解法检测黑素含量.结果 CLEC2B基因过表达的Jurkat细胞培养上清液作用后的黑素瘤细胞增殖比空载体组、正常对照组降低,差异有统计学意义(均P<0.05),CLEC2B过表达组黑素含量比空载体组、正常对照组减少,差异有统计学意义(均P<0.05),CLEC2B过表达组、空载体组、正常对照组之间的酪氨酸酶活性比较差异无统计学意义(均P>0.05),空载体组与正常对照组比较差异均无统计学意义(均P>0.05).结论 CLEC2B基因过表达的Jurkat细胞培养上清液对黑素细胞的增殖和黑素合成有一定的抑制作用,对酪氨酸酶活性影响不明显.提示CLEC2B可能通过调节淋巴细胞功能间接影响黑素细胞增殖和黑素合成,从而参与白癜风发病.%Objective The melanoma cells were treated with culture supernatant of CLEC2B gene overexpression in Jurkat cells, to observe the impact of melanoma proliferation, the activity of tyrosinase and melanin synthesis, for searching CLEC2B gene participated in the vitiligo. Methods In this study, Jurkat cells were transfected with recombinant plasmid pGCMV/EGFP/Neo-CLEC2B by DMRIE-C Reagent. RT-PCR identified CLEC2B gene overexpression. After 48 h transfection, the melanoma cells were treated with their culture supernatant for 48 h, then the proliferation of melanoma cells were detected by MTT, the activity of tyrosinase was detected by

  18. Synergistic defense system by cooperative natural effectors against metastasis of B16 melanoma cells in H-2-associated control: different behavior of H-2+ and H-2- cells in metastatic processes

    International Nuclear Information System (INIS)

    H-2+ and H-2- cells of B16 melanoma were established by repeated fluorescence-activated cell sorting. The H-2- line formed no metastasis in untreated C57BL/6 mice, whereas the H-2+ cells showed evidence of metastatic development. This difference was ascribed mainly to the increased susceptibility of H-2- cells to attack by natural effector mechanisms, particularly asialo GM1+ NK cells. After treatment with both anti-asialo GM1 serum and whole body irradiation (400 rad), numerous colonies of H-2- cells formed in the lung, whereas the metastasis was only marginally enhanced by irradiation and moderately by treatment with anti-asialo GM1 serum. With the H-2+ cells, treatment with each modality significantly increased the number of metastatic colonies. Therefore collaboration of asialo GM1+ NK cells and radiosensitive natural effectors seems to be the main mechanism involved in the synergistic effects on defense against H-2- cell metastasis, and to a lesser extent against H-2+ cell metastasis. Irradiation (1000 rad) to the right lung to abrogate the organ-associated defense increased the colonies, particularly in the H-2+ cells. On the other hand, treatment with anti-asialo GM1 serum increased colonization in the early phase of metastasis with H-2- cells and may have abolished asialo GM1+ NK cells capable of recognizing the reduced expression of H-2 antigens and eliminating H-2- cells in the blood-born phase. Natural defense mechanisms probably exert suppressive effects on the metastasis of H-2+ cells, mainly in the organ-associated phase after extravasation

  19. Chlorpromazine distribution in hamsters and mice bearing transplantable melanoma

    International Nuclear Information System (INIS)

    Chlorpromazine (CPZ) distribution was measured in tissues of Syrian golden hamsters bearing Greene melanoma and in BALB/c mice bearing Harding-Passey melanoma. Distribution was evaluated as a function of time (0.5 to 14 days) and as a function of single and multiple doses (up to five) of from 5 to 50 mg CPZ per kg body weight. Routes of administration (i.p., i.v., p.o.) were compared. The physiological behavior of CPZ is of interest as it is used extensively as a tranquilizing drug (Thorazine). Further, since CPZ binds to the pigment melanin, the possibility exists of using CPZ to transport diagnostic or therapeutic agents to melanoma. It was found that, at 2 days postinjection, tumor/tissue concentration ratios exceeded 10 for metabolizing organs, such as liver, and 100 for background tissues, such as blood and muscle. Absolute concentrations of CPZ in tumor exceeding 100 μg CPZ per g tumor were obtained with both single and multiple doses. This selective high concentration in tumor would make CPZ an ideal vehicle for the transport of boron to tumor for use in neutron capture therapy via the 10B(n,α)7Li reaction

  20. 复方木尼孜其颗粒对小鼠B16黑素瘤细胞酪氨酸酶活性及黑素合成的影响%Effects of Fufang Muniziqi Particle on Melanin Synthesis and Tyrosinase Activity in Mouse B16 Melanoma Cells

    Institute of Scientific and Technical Information of China (English)

    纪超; 毕志刚

    2014-01-01

    目的 研究复方木尼孜其颗粒对小鼠B16黑素瘤细胞酪氨酸酶活性及黑素合成的影响.方法 培养小鼠B16黑素瘤细胞,采用MTT法测定不同浓度复方木尼孜其颗粒对细胞增殖的影响,采用L-DOPA氧化法测定其对细胞酪氨酸酶活性的影响,采用NaOH裂解法检测细胞黑素含量.结果 复方木尼孜其颗粒高剂量组能明显抑制小鼠B16黑素瘤细胞黑素的合成,但是对酪氨酸酶活性无影响.结论 复方木尼孜其颗粒能抑制小鼠B16黑素瘤细胞黑素的合成,在治疗色素性皮肤病中有一定前景.

  1. 杏仁油对黑色素瘤细胞B16细胞增殖及黑素合成的影响%Effects of Almond Kernel Oil on Cell Proliferation and Melanin Synthesis of Cultured B16 Murine Melanoma Cell

    Institute of Scientific and Technical Information of China (English)

    任燕冬; 宋宏杉; 陈巧云; 张宁

    2011-01-01

    目的 探讨杏仁油对小鼠黑色素瘤细胞B16增殖及黑素合成的影响.方法 采用MTT法测定杏仁油对小鼠黑色素瘤细胞B16增殖的影响,L-dopa氧化法测定酪氨酸酶活性,NaOH裂解法测定黑素合成.结果 杏仁油浓度在0.1~100μg/mL时对小鼠黑色素瘤细胞B16增殖无影响(P>0.05),对酪氨酸酶活性和黑素含量均呈浓度依赖性抑制,均具有显著性抑制作用(P<0.05).结论 杏仁油对黑色素瘤细胞B16酪氨酸酶活性和黑素生成有较强的剂量相关性抑制作用.

  2. Growth of transplantable melanoma and leukaemia and prevention of virus-induced leukaemia in long lived radiation chimeras constructed with unmanipulated bone marrow

    International Nuclear Information System (INIS)

    Haemopoietic radiation chimeras across the H-2 barrier (BALB/c → C57B1/6; H-2sup(d) → H-2sup(b) chimeras and vice versa) have been studied for their capacity to suppress the growth, or to reject, transplantable B16 melanotic melanoma and radiation leukaemia virus-induced, transplantable leukaemia. Also, radiation leukaemia virus (RadLV) obtained from the thymus of leukaemic C57B1/6 mice was injected i.p. into established chimeras (H-2sup(d) → H-2sup(b)). As expected, long lived, graft versus host disease free allogeneic chimeras constructed with intact bone marrow were unable to reject the tumours both when recipients were BALB/c → C57B1/6 or C57B1/6 → BALB/c chimeras. However, inoculation of a large number of immunocompetent cells from normal BALB/c mice into BALB/c → C57B1/6 chimeras failed to promote a rejection of the tumours. On the contrary, the same amount of syngeneic (BALB/c) immunocompetent cells prevented growth of melanoma when transferred into athymic nude BALB/c mice, while the tumour grew unimpaired in untreated athymic nude BALB/c mice. The same type of H-2sup(d) → H-2sup(b) chimeras displayed complete resistance to inoculation of leukaemogenic H-2sup(b) restricted RadLV while all H-2sup(b) → H-2sup(b), syngeneically reconstituted mice developed disseminated leukaemia. (author)

  3. Overview on non-melanoma skin cancers in solid organ transplant recipients.

    Science.gov (United States)

    Forchetti, G; Suppa, M; Del Marmol, V

    2014-08-01

    The risk of non-melanoma skin cancer (NMSC) is significantly increased in solid organ transplant recipients (SOTRs) due to the long-term immunosuppressive treatment. NMSCs can be more aggressive in SOTRs than in the general population, resulting in significantly higher morbidity and mortality. In contrast to the immunocompetent population, skin cancers in SOTRs are dominated by squamous cell carcinoma, followed by basal cell carcinoma. Life-long radiation exposure, male sex, fair skin, history of prior NMSC, genetic factors, age at transplant along with duration and extent of the immunosuppression therapy have been identified as risk factors for NMSC in SOTRs. Photo-protection, skin self-examination, early diagnosis and treatment of skin lesions, reduction of immunotherapy, switch to mammalian target-of-rapamycin inhibitors and chemoprevention with oral retinoids are effective measures for the reduction of the incidence of NMSC in such patients. PMID:25068224

  4. Human melanoma cells transplanted into zebrafish proliferate, migrate, produce melanin, form masses and stimulate angiogenesis in zebrafish.

    Science.gov (United States)

    Haldi, Maryann; Ton, Christopher; Seng, Wen Lin; McGrath, Patricia

    2006-01-01

    In this research, we optimized parameters for xenotransplanting WM-266-4, a metastatic melanoma cell line, including zebrafish site and stage for transplantation, number of cells, injection method, and zebrafish incubation temperature. Melanoma cells proliferated, migrated and formed masses in vivo. We transplanted two additional cancer cell lines, SW620, a colorectal cancer cell line, and FG CAS/Crk, a pancreatic cancer cell line and these human cancers also formed masses in zebrafish. We also transplanted CCD-1092Sk, a human fibroblast cell line established from normal foreskin and this cell line migrated, but did not proliferate or form masses. We quantified the number of proliferating melanoma and normal skin fibroblasts by dissociating xenotransplant zebrafish, dispensing an aliquot of CM-DiI labeled human cells from each zebrafish onto a hemocytometer slide and then visually counting the number of fluorescently labeled cancer cells. Since zebrafish are transparent until approximately 30 dpf, the interaction of labeled melanoma cells and zebrafish endothelial cells (EC) can be visualized by whole-mount immunochemical staining. After staining with Phy-V, a mouse anti-zebrafish monoclonal antibody (mAb) that specifically labels activated EC and angioblasts, using immunohistology and 2-photon microscopy, we observed activated zebrafish EC embedded in human melanoma cell masses. The zebrafish model offers a rapid efficient approach for assessing human cancer cells at various stages of tumorigenesis. PMID:17051341

  5. An ethical dilemma: malignant melanoma in a 51-year-old patient awaiting simultaneous kidney and pancreas transplantation for type 1 diabetes.

    Science.gov (United States)

    Kirby, L C; Banerjee, A; Augustine, T; Douglas, J F

    2016-07-01

    Malignant melanoma is a high-risk skin cancer that, in potential transplant recipients, is considered a substantial contraindication to solid organ transplantation due to significant risk of recurrence with immunosuppression. Current guidelines stipulate waiting between 3 and 10 years after melanoma diagnosis. However, in young patients with end-stage organ failure and malignant melanoma, complex ethical and moral issues arise. Assessment of the true risk associated with transplantation in these patients is difficult due to lack of prospective data, but an autonomous patient can make a decision that clinicians may perceive to be high risk. The national and worldwide shortage of available organs also has to be incorporated into the decision to maximize the net benefit and minimize the risk of graft failure and mortality. The incidence of malignant melanoma worldwide is increasing faster than that of any other cancer and continues to pose ethically challenging decisions for transplant specialists evaluating recipients for solid organ transplantation. PMID:27484276

  6. Melanoma

    Science.gov (United States)

    ... may be melanoma is the ABCDE checklist: A – Asymmetry: One half of the mole does not look ... 276. PMID: 16050450. Last Updated: 12 Feb 2009 Information for other ages: Table of Contents: Overview Who's ...

  7. 鱿鱼皮胶原蛋白多肽对B16黑素瘤细胞黑素合成的影响%Effects of collagen polypeptides from squid (Dosidicus gigas)skin on melanogenesis in B16 melanoma cells

    Institute of Scientific and Technical Information of China (English)

    王静凤; 王奕; 崔凤霞; 李八方; 薛长湖

    2007-01-01

    目的 研究不同分子量鱿鱼皮胶原蛋白多肽SP1(Mr>10 000u)、SP2(6 000u<Mr<10 000u)、SP3(2 000u<Mr<6 000u)对小鼠B16黑素瘤细胞黑素含量、酪氨酸酶活性及酪氨酸酶基因表达的影响.方法 采用MTT法测定细胞增殖活性,NaOH裂解法测定黑素含量,多巴氧化法测定酪氨酸酶活性,逆转录-聚合酶链反应(RT-PCR)测定酪氨酸酶mRNA表达.结果 不同分子量鱿鱼皮胶原蛋白多肽均能明显降低B16黑素瘤细胞黑素含量(P<0.05,P<0.01),抑制酪氨酸酶活性(P<0.01),并下调酪氨酸酶mRNA表达(P<0.05,P<0.01),且剂量效应关系明显.结论 不同分子量鱿鱼皮胶原蛋白多肽均具有明显抑制B16黑素瘤细胞黑素合成的作用,其中SP2的抑制效果较SP1、SP3明显(P<0.05).

  8. Depleción de GSH y Bcl-2 en células de melanoma maligno B16: mecanismos de sensibilización frente al estrés oxidativo/nitrosativo y la quimioterapia.

    OpenAIRE

    Benlloch García, María

    2008-01-01

    RESUMEN Introducción: La causa de muerte de la mayoría de los enfermos de cáncer es la metástasis de células tumorales. El melanoma es un modelo muy utilizado para el estudio de la progresión del tumor. La supervivencia y crecimiento de células de MB16 metastáticas está directamente relacionado con el aumento de su contenido en glutatión (GSH). Además dichas células sobreexpresan Bcl-2, mostrando un incremento de GSH sin mostrar un aumento en su síntesis pero sí una disminución en la...

  9. Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC).

    Science.gov (United States)

    Zwald, F; Leitenberger, J; Zeitouni, N; Soon, S; Brewer, J; Arron, S; Bordeaux, J; Chung, C; Abdelmalek, M; Billingsley, E; Vidimos, A; Stasko, T

    2016-02-01

    Advancements in solid organ transplantation successfully extend the lives of thousands of patients annually. The tenet of organ stewardship aims to prevent the futile expenditure of scarce donor organs in patient populations with high mortality risk, to the detriment of potential recipients with greater predicted life expectancy. The development of skin cancer posttransplantation portends tremendous morbidity, adversely affecting quality of life for many transplant recipients. This special article, provided by of members of the International Transplant Skin Cancer Collaborative (ITSCC), will provide the transplant professional with a consensus opinion and recommendations as to an appropriate wait period pretransplantation for transplant candidates with a history of either cutaneous squamous cell carcinoma, malignant melanoma, or Merkel cell carcinoma. PMID:26820755

  10. Role of radiotherapy in the management of organ transplant recipients diagnosed with non-melanoma skin cancers

    International Nuclear Information System (INIS)

    Organ transplantation has had a major effect on the lives of thousands of patients worldwide. In Australia and New Zealand, over 13 000 patients have become organ transplant recipients (OTR). Following transplantation, patients require lifelong immunosuppression to prevent organ rejection. The loss of immune surveillance results in OTR experiencing a higher incidence of infection and malignancy in comparison with the general (immunocompetent) population. Non-melanoma skin cancer (NMSC) is the most common malignancy worldwide, arising most often on the sun-exposed head and neck. Organ transplant recipients experience a higher incidence of NMSC when compared with the general population and a higher incidence of squamous cell carcinoma compared with basal cell carcinoma. Organ transplant recipients also develop NMSC at a younger age and experience multiple new NMSC. Australians experience the highest incidence of NMSC in the world with a consequence that NMSC arising in OTR can lead to significant morbidity and even mortality. Radiation oncologists treating patients with skin cancer will almost certainly make recommendations in the setting of NMSC arising in OTR. The aim of this article is to discuss the role of radiotherapy in the management of OTR diagnosed with NMSC. The emphasis will be on the treatment of patients with a high-risk NMSC (e.g. squamous cell carcinoma, Merkel cell carcinoma, unfavourable basal cell carcinoma) because this reflects the most common clinical scenario in which a recommendation of radiotherapy, usually adjuvant, may be considered

  11. 15 CFR 8b.16 - Discrimination prohibited.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Discrimination prohibited. 8b.16 Section 8b.16 Commerce and Foreign Trade Office of the Secretary of Commerce PROHIBITION OF DISCRIMINATION... Accessibility § 8b.16 Discrimination prohibited. No qualified handicapped individual shall, because a...

  12. Antitumoral, antioxidant, and antimelanogenesis potencies of Hawthorn, a potential natural agent in the treatment of melanoma.

    Science.gov (United States)

    Mustapha, Nadia; Mokdad-Bzéouich, Imèn; Maatouk, Mouna; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

    2016-06-01

    The lack of an efficient agent that does not have the disadvantage of low activity (kojic acid), high cytotoxicity, and mutagenicity (hydroquinone), poor skin penetration (arbutin), or low stability in formulation (glabridin) led us to continue our research on new antipigmentation/skin-lightening agents. Therefore, research of natural products that can modulate the metabolism of pigmentation is of great interest. Otherwise, malignant melanoma is one of the most aggressive forms of skin cancer, with high metastatic potential, and currently, there is no effective chemotherapy against invasive melanoma. Therefore, it is necessary to develop new drugs with potent activity and weak side effects against melanoma. The in-vitro anticancer effect of hawthorn was analyzed against B16F10 melanoma cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of isolated compounds from hawthorn on melanogenesis in B16F10 melanoma cells was investigated by measuring the amounts of melanin and tyrosinase spectrophotometrically at 475 nm. Balb/c mice models inoculated with B16F10 mouse tumor cells were used to evaluate the in-vivo antitumoral potential of hawthorn by assessing its effect on the growth of transplanted tumors. The antioxidant potential of tested samples was evaluated in B16F10 and primary human keratinocyte cells using a cellular antioxidant activity assay. Hawthorn tested samples inhibited effectively the growth of melanoma cells in vitro. Furthermore, it appears that tested samples from hawthorn reduced melanogenesis by inhibiting the tyrosinase activity of B16F10 cells in a dose-dependent manner. In-vivo studies showed that hawthorn total oligomer flavonoids extract treatment at a dose of 150 mg/kg body weight for 21 days in implanted tumor mice resulted in significant inhibition of the tumor growth volume and weight. In addition, tested samples showed significant cellular antioxidant capacity against the reactive oxygen species

  13. Lentivirus-mediated bifunctional cell labeling for in vivo melanoma study.

    Science.gov (United States)

    Day, Chi-Ping; Carter, John; Bonomi, Carrie; Esposito, Dominic; Crise, Bruce; Ortiz-Conde, Betty; Hollingshead, Melinda; Merlino, Glenn

    2009-06-01

    Lentiviral vectors (LVs) are capable of labeling a broad spectrum of cell types, achieving stable expression of transgenes. However, for in vivo studies, the duration of marker gene expression has been highly variable. We have developed a series of LVs harboring different promoters for expressing reporter gene in mouse cells. Long-term culture and colony formation of several LV-labeled mouse melanoma cells showed that promoters derived from mammalian house-keeping genes, especially those encoding RNA polymerase II (Pol2) and ferritin (FerH), provided the highest consistency for reporter expression. For in vivo studies, primary B16BL6 mouse melanoma were infected with LVs whose luciferase-green fluorescence protein fusion gene (Luc/GFP) was driven by either Pol2 or FerH promoters. When transplanted into syngeneic C57BL/6 mice, Luc/GFP-labeled B16BL6 mouse melanoma cells can be monitored by bioluminescence imaging in vivo, and GFP-positive cells can be isolated from the tumors by fluorescence-activated cell sorter. Pol2-Luc/GFP labeling, while lower in activity, was more sustainable than FerH-Luc/GFP labeling in B16BL6 over consecutive passages into mice. We conclude that Pol-2-Luc/GFP labeling allows long-term in vivo monitoring and tumor cell isolation in immunocompetent mouse melanoma models. PMID:19175523

  14. Melanoma of the eye

    Science.gov (United States)

    ... modified July 9, 2015. www.cancer.gov/types/eye/hp/intraocular-melanoma-treatment-pdq . Accessed October 7, 2015. Read ... by: Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital, Boston, MA. Also reviewed ...

  15. Radioiodinated N-(alkylaminoalkyl)-substituted 4-methoxy-, 4-hydroxy-, and 4-aminobenzamides: Biological investigations for the improvement of melanoma-imaging agents

    International Nuclear Information System (INIS)

    The synthesis and radiolabeling of 27 new N-(alkylaminoalkyl)-4-methoxy-, 4-hydroxy-, and -4-aminobenzamides are described and evaluated in C57Bl/6 mice with subcutaneously transplanted B16 melanoma in order to screen the optimal chemical structure for melanoma scintigraphy. Using Tl(TFA)3 for 131I- labeling, a series of radioiodinated 4-methoxy benzamide derivatives proved to exhibit superior melanoma uptake with outstanding melanoma/non-target-tissue ratios. From the benzamide derivatives tested, N-(2-(1'-piperidinyl)ethyl)-3-[131I]iodo-4-methoxybenzamide (1) and N-(2-diethylaminoethyl)-3-[131I]iodo-4-methoxybenzamide (2) demonstrated best results. The introduction of 4-hydroxy and 4-amino groups led to less favourable benzamides. While the former compounds showed little melanoma uptake, the latter revealed unfavourable melanoma/non-target-tissue ratios. Additionally, it could be shown that an amino group was inevitably necessary for melanoma uptake, and that dialkylation of the amide nitrogen and replacing CONH by CH2NH revealed less advantageous results

  16. Targeting B16 tumors in vivo with peptide-conjugated gold nanoparticles

    Science.gov (United States)

    Poon, Wilson; Zhang, Xuan; Bekah, Devesh; Teodoro, Jose G.; Nadeau, Jay L.

    2015-07-01

    This study examines the effects of polyethylene glycol (PEG) and peptide conjugation on the biodistribution of ultrasmall (2.7 nm) gold nanoparticles in mice bearing B16 melanoma allografts. Nanoparticles were delivered intravenously, and biodistribution was measured at specific timepoints by organ digestion and inductively coupled plasma mass spectrometry. All major organs were examined. Two peptides were tested: the cyclic RGD peptide (cRGD, which targets integrins); and a recently described peptide derived from the myxoma virus. We found the greatest specific tumor delivery using the myxoma peptide, with or without PEGylation. Un-PEGylated cRGD performed poorly, but PEGylated RGD showed a significant transient collection in the tumor. Liver and kidney were the primary targets of all constructs. None of the particles were able to cross the blood-brain barrier. Although it was able to deliver Au to B16 cells, the myxoma peptide did not show any cytotoxic activity against these cells, in contrast to previous reports. These results indicate that the effect of passive targeting by PEGylation and active targeting by peptides can be independent or combined, and that they should be evaluated on a case-by-case basis when designing new nanosystems for targeted therapies. Both myxoma peptide and cRGD should be considered for specific targeting to melanoma, but a thorough investigation of the cytotoxicity of the myxoma peptide to different cell lines remains to be performed.

  17. Transplantation.

    Science.gov (United States)

    Faro, Albert; Weymann, Alexander

    2016-08-01

    Despite improvement in median life expectancy and overall health, some children with cystic fibrosis (CF) progress to end-stage lung or liver disease and become candidates for transplant. Transplants for children with CF hold the promise to extend and improve the quality of life, but barriers to successful long-term outcomes include shortage of suitable donor organs; potential complications from the surgical procedure and immunosuppressants; risk of rejection and infection; and the need for lifelong, strict adherence to a complex medical regimen. This article reviews the indications and complications of lung and liver transplantation in children with CF. PMID:27469184

  18. Enucleaton of the right eye due to large choroidal melanoma with simultaneous penetrating cornea transplantation from OD to OS (Case report.

    Directory of Open Access Journals (Sweden)

    E. A. Korchuganova

    2013-01-01

    Full Text Available There is presentation case report of 75‑year old woman with choroidal melanoma (T3N0M0 on the right eye and failed graft on the left pseudophakic eye with far advanced glaucoma and ARMD. No treatment was given to the leading eye with VA 0,2. VA of OS = 1 / ∞ pr.l.certa; PKP OS in 2008 for pseudophakic bullous keratopathy on the eye with far advanced glaucoma. IOP was normal after previous filtering surgery. After PKP VA = 0,04; clear graft during 2 years; then gradually opacification and vascularization occurred. VA dropped to light perception. Echography OD — tumor h 8,29 mm, d 21,77 mm. No ingrowth of tumor into anterior segment of the eye; VA OD = 0 (no light perception. Concerning the need to enucleate the right eye with large choroidal melanoma, the advantage of using corneal autograft from OD to OS, location of tumor in the posterior pole with no ingrowth in anterior segment, the decision was made to perform the following operation — to enucleate the right eye and transplant simultaneously corneal graft from OD on OS. Patient was discharged from the Ophthalmology Hospital with VA OS = 0,01, during next week VA improved to 0,02. 8,0 mm graft isclear, fixed with 8 interruptured and continious suture 10 / 0‑nylon. Anterior chamber — normal depth, atrophic iris, stable position of PC IOL. Optic nerve head is pale with subtotal deep glaucomatous excavation. Conclusion: presented case report demonstrates the rarepossibility to use cornea after enucleation the eye with large malignant tumor (located in the posterior pole for grafting in the only eye with failed vascularised graft. It was the only possibility for this patient to restore some vision.

  19. Enucleaton of the right eye due to large choroidal melanoma with simultaneous penetrating cornea transplantation from OD to OS (Case report.

    Directory of Open Access Journals (Sweden)

    E. A. Korchuganova

    2014-07-01

    Full Text Available There is presentation case report of 75‑year old woman with choroidal melanoma (T3N0M0 on the right eye and failed graft on the left pseudophakic eye with far advanced glaucoma and ARMD. No treatment was given to the leading eye with VA 0,2. VA of OS = 1 / ∞ pr.l.certa; PKP OS in 2008 for pseudophakic bullous keratopathy on the eye with far advanced glaucoma. IOP was normal after previous filtering surgery. After PKP VA = 0,04; clear graft during 2 years; then gradually opacification and vascularization occurred. VA dropped to light perception. Echography OD — tumor h 8,29 mm, d 21,77 mm. No ingrowth of tumor into anterior segment of the eye; VA OD = 0 (no light perception. Concerning the need to enucleate the right eye with large choroidal melanoma, the advantage of using corneal autograft from OD to OS, location of tumor in the posterior pole with no ingrowth in anterior segment, the decision was made to perform the following operation — to enucleate the right eye and transplant simultaneously corneal graft from OD on OS. Patient was discharged from the Ophthalmology Hospital with VA OS = 0,01, during next week VA improved to 0,02. 8,0 mm graft isclear, fixed with 8 interruptured and continious suture 10 / 0‑nylon. Anterior chamber — normal depth, atrophic iris, stable position of PC IOL. Optic nerve head is pale with subtotal deep glaucomatous excavation. Conclusion: presented case report demonstrates the rarepossibility to use cornea after enucleation the eye with large malignant tumor (located in the posterior pole for grafting in the only eye with failed vascularised graft. It was the only possibility for this patient to restore some vision.

  20. Control of differentiation of melanoma cells

    International Nuclear Information System (INIS)

    To develop the method to induce the appearance of differentiation in amelanotic melanoma, experimental control of differentiation in B-16 melanoma cells of mice was discussed. Human melanoma cells and yellow melanin pigment cells useful for a fundamental study of radiotherapy for cancer were cultured and were differentiated into some lines. Melanotic B-16 cells and amelanotic B-16 cells were irradiated with thermal neutron (neutron: 2.7 x 1012, γ-dose: 32.3 rad) after they were cultured in culture solution containing 10 γ/ml of 10B-dopa for 13 hours. A fine structure 5 hours after the irradiation in one of 5 experimental cases showed aggregated disintegration of melanin pigment particles, markedly deformed and fragmentized nucleus, and structural changes in cell membrane. (Tsunoda, M.)

  1. Radiopharmaceuticals targeting melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Pham, T.Q.; Berghofer, P.; Liu, X.; Greguric, I.; Dikic, B.; Ballantyne, P.; Mattner, F.; Nguyen, V.; Loc' h, C.; Katsifis, A. [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Menai, N.S.W., Sydney (Australia)

    2008-02-15

    Melanoma is one of the most aggressive cancers known with a high rate of mortality and increasing global incidence. So, the development of radiopharmaceuticals for either diagnostic or therapeutic purposes could make enormous contributions to melanoma patient health care. We have been studying melanoma tumours through several targeting mechanisms including melanin or specific receptor based radiopharmaceuticals Structure activity studies indicate that the substitution patterns on radioiodinated benzamides significantly influence the uptake mechanism from melanin to sigma-receptor binding. Furthermore, the position of the iodine as well as the presence of key functional groups and substituents has resulted in compounds with varying degrees of activity uptake and retention in tumours. From these results, a novel molecule 2-(2-(4-(4-iodo benzyl)piperazin-1-yl)-2-oxo-ethyl)isoindoline- 1,3-dione (M.E.L.037) was synthesized, labelled with iodine-123 and evaluated for application in melanoma tumour scintigraphy and radiotherapy. The tumour imaging potential of {sup 123}IM.E.L.037 was studied in vivo in C.57 B.L./ 6 J female mice bearing the B.16 F.0. murine melanoma tumour and in BALB/c nude mice bearing the A.375 human amelanotic melanoma tumour by biodistribution, competition studies and by SPECT imaging. {sup 123}I-M.E.L.037 exhibited high and rapid uptake in the B.16 F.0 melanoma tumour at 1 h (13 % I.D./g) increasing with time to reach 25 % I.D./g at 6 h. A significant uptake was also observed in the eyes (2% I.D., at 3-6 h p.i.) of black mice. No uptake was observed in the tumour or in the eyes of nude mice bearing the A.375 tumour. Due to high uptake and long retention in the tumour and rapid body clearance, standardized uptake values(S.U.V.) of {sup 123}I-M.E.L.037 were 30 and 60, at 24 and 48 h p.i.,respectively. SPECT imaging of mice bearing the B.16 melanoma indicated the radioactivity was predominately located in the tumour followed by the eyes, while no

  2. Tumor vaccine strategies after allogeneic T-cell depleted bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Ferrara James L.M.

    2002-01-01

    Full Text Available Allogeneic bone marrow transplantation is currently restricted to hematological malignancies because of a lack of anti-tumor activity against solid cancers. We have tested a novel treatment strategy to stimulate specific anti-tumor activity against a solid tumor after transplantation by vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor. Using the B16 melanoma model, we found that vaccination elicited potent anti-tumor activity in recipients of syngeneic bone marrow transplantation in a time dependent fashion, and that immune reconstitution was critical for the development of anti-tumor activity. Vaccination did not stimulate anti-tumor immunity after allogeneic bone marrow transplantation because of the post-transplantation immunodeficiency associated with graft-versus-host disease. Remarkably, vaccination was effective in stimulating potent and long-lasting anti-tumor activity in recipients of T cell-depleted allogeneic bone marrow. Thus T cells derived from donor stem cells were able to recognize tumor antigens even though they remained tolerant to host histocompatibility antigens. Donor leukocyte infusion from a donor immunized with the recipient-derived B16 vaccines enhanced clinical activity of tumor vaccines without exacerbating graft-versus-host disease and CD4+ T cells are essential for this enhancement. These results demonstrate that vaccination of both donors and recipients can stimulate potent anti-tumor effects without the induction of graft-versus-host disease, and this strategy has important implications for the treatment of patients with solid malignancies.

  3. TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    Objective: To explore the experience ofliver transpfantation in patients with terminalliver failure. Methods: From October 1991 toJuly 1995, 17 adults and 6 children underwentorthotopic liver transplantation. Preoperativediagnosis showed biliary atresia (n=5), Alagillesyndrome (n=1), primary biliary cirrhosis(n=2), cryptogenic cirrhosis (n=2), alcoholic

  4. Effects of Wnt-10b on proliferation and differentiation of murine melanoma cells

    International Nuclear Information System (INIS)

    In spite of the strong expression of Wnt-10b in melanomas, its role in melanoma cells has not been elucidated. In the present study, the biological effects of Wnt-10b on murine B16F10 (B16) melanoma cells were investigated using conditioned medium from Wnt-10b-producing COS cells (Wnt-CM). After 2 days of culture in the presence of Wnt-CM, proliferation of B16 melanoma cells was inhibited, whereas tyrosinase activity was increased. An in vitro wound healing assay demonstrated that migration of melanoma cells to the wound area was inhibited with the addition of Wnt-CM. Furthermore, evaluation of cellular senescence revealed prominent induction of SA-β-gal-positive senescent cells in cultures with Wnt-CM. Finally, the growth of B16 melanoma cell aggregates in collagen 3D-gel cultures was markedly suppressed in the presence of Wnt-CM. These results suggest that Wnt-10b represses tumor cell properties, such as proliferation and migration of B16 melanoma cells, driving them toward a more differentiated state along a melanocyte lineage. - Highlights: • Wnt-10b inhibited proliferation and migration of melanoma cells. • Wnt-10b induced tyrosinase activity and senescence of melanoma cells. • Wnt-10b suppressed growth of cell aggregates in collagen 3D-gel cultures. • Wnt-10b represses tumor cell properties, driving them toward a more differentiated state along a melanocyte lineage

  5. Effects of Wnt-10b on proliferation and differentiation of murine melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Misu, Masayasu [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ouji, Yukiteru, E-mail: oujix@naramed-u.ac.jp [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Kawai, Norikazu [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Nishimura, Fumihiko [Department of Neurosurgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Nakamura-Uchiyama, Fukumi [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Yoshikawa, Masahide, E-mail: myoshika@naramed-u.ac.jp [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan)

    2015-08-07

    In spite of the strong expression of Wnt-10b in melanomas, its role in melanoma cells has not been elucidated. In the present study, the biological effects of Wnt-10b on murine B16F10 (B16) melanoma cells were investigated using conditioned medium from Wnt-10b-producing COS cells (Wnt-CM). After 2 days of culture in the presence of Wnt-CM, proliferation of B16 melanoma cells was inhibited, whereas tyrosinase activity was increased. An in vitro wound healing assay demonstrated that migration of melanoma cells to the wound area was inhibited with the addition of Wnt-CM. Furthermore, evaluation of cellular senescence revealed prominent induction of SA-β-gal-positive senescent cells in cultures with Wnt-CM. Finally, the growth of B16 melanoma cell aggregates in collagen 3D-gel cultures was markedly suppressed in the presence of Wnt-CM. These results suggest that Wnt-10b represses tumor cell properties, such as proliferation and migration of B16 melanoma cells, driving them toward a more differentiated state along a melanocyte lineage. - Highlights: • Wnt-10b inhibited proliferation and migration of melanoma cells. • Wnt-10b induced tyrosinase activity and senescence of melanoma cells. • Wnt-10b suppressed growth of cell aggregates in collagen 3D-gel cultures. • Wnt-10b represses tumor cell properties, driving them toward a more differentiated state along a melanocyte lineage.

  6. Highly diluted compounds effects on B16-F10 melanogenesis, reactive oxygen species (ROS production and tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Edvaldo da Silva Trindade

    2012-09-01

    Full Text Available Background: Cutaneous melanoma is a highly malignant tumor derived from pigment-producing (melanin melanocytes of skin epidermis. Cutaneous pigmentation is described as the major physiologic defense against UV radiation. During melanin biosynthesis and other tumorigenic process, reactive oxygen species (ROS are produced and might be critically involved in several melanomagenesis stages. ROS play key roles on regulation of many types cell proliferation, including melanoma cells. Aims: In this work we evaluated the effects of highly diluted compounds on melanogenesis and changes in reactive oxygen species after 96 hours of treatment and possible involvement in tumorigenesis. Methodology: Melanin content was measured in B16-F10 cells after 96 hours of treatment with highly diluted compounds, as well as the superoxide anion, hydrogen peroxide and nitric oxide. Furthermore, the effects of highly diluted compounds on cell proliferation were investigated by trypan blue exclusion method after 48 hours of treatment. Results: Treatment led to an increase in B16-F10 melanin content and a decrease in nitrite concentration, an intermediate product of nitric oxide. We also observed a decrease in cell proliferation after treatment. It is well recognized that nitric oxide (NO is involved in tumor progression, including melanoma. Several articles show that NO treated B16-F10 cells exhibited higher metastatic capacity. Thereby, reduction in cell proliferation can be due to low NO levels. It is speculated that melanocytes are programmed to survive in order to preserve their photoprotective role, thus in a compensatory manner the cell may be synthesizing melanin in response to cell proliferation reduction. Conclusions: These results suggest that treatment may be reducing tumorigenic capacity via ROS reduction. However further studies are need to better understand highly diluted compounds mechanisms of action.

  7. Lumican Inhibits SNAIL-Induced Melanoma Cell Migration Specifically by Blocking MMP-14 Activity

    Science.gov (United States)

    Stasiak, Marta; Boncela, Joanna; Perreau, Corinne; Karamanou, Konstantina; Chatron-Colliet, Aurore; Proult, Isabelle; Przygodzka, Patrycja; Chakravarti, Shukti; Maquart, François-Xavier; Kowalska, M. Anna; Wegrowski, Yanusz; Brézillon, Stéphane

    2016-01-01

    Lumican, a small leucine rich proteoglycan, inhibits MMP-14 activity and melanoma cell migration in vitro and in vivo. Snail triggers epithelial-mesenchymal transitions endowing epithelial cells with migratory and invasive properties during tumor progression. The aim of this work was to investigate lumican effects on MMP-14 activity and migration of Snail overexpressing B16F1 (Snail-B16F1) melanoma cells and HT-29 colon adenocarcinoma cells. Lumican inhibits the Snail induced MMP-14 activity in B16F1 but not in HT-29 cells. In Snail-B16F1 cells, lumican inhibits migration, growth, and melanoma primary tumor development. A lumican-based strategy targeting Snail-induced MMP-14 activity might be useful for melanoma treatment. PMID:26930497

  8. The effect of antineoplastic drug NSC631570 on immunogenicity of B16 melanoma

    OpenAIRE

    Skivka, Larysa M.; Olexander G. Fedorchuk; Natalia O. Bezdeneznykh; Olexanrda O. Lykhova; Nadija I. Semesiuk; Yuri I. Kudryavets; Oksana M. Malanchuk

    2014-01-01

    Objectives: NSC631570 is a cytotoxic drug with the ability to be selectively accumulated in tumor tissue and activate apoptosis only in malignant cells and not in normal cells. Therapy with NSC631570 is accompanied by the stimulation of anticancer immune responses. It is known that cytotoxic anticancer drugs have additional effects on the immune system of tumor-bearing organism by increasing the immunogenic properties of tumor cells. This study aimed to investigate the immunogenicity of melan...

  9. Electrochemotherapy by pulsed electromagnetic field treatment (PEMF in mouse melanoma B16F10 in vivo

    Directory of Open Access Journals (Sweden)

    Kranjc Simona

    2016-03-01

    Full Text Available Pulsed electromagnetic field (PEMF induces pulsed electric field, which presumably increases membrane permeabilization of the exposed cells, similar to the conventional electroporation. Thus, contactless PEMF could represent a promising approach for drug delivery.

  10. Inhibitory activity of Bifidobacterium adolescent combined with cisplatin on melanoma in mice and its mechanism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The aim of this study is to explore inhibitory activity of Bifidobacterium adolescent combined with cisplatin on the growth of melanoma(B16)in mice and the underlying mechanism.C57 mice were inoculated with B16 cancer cells to construct mouse model of melanoma and treated with bifidobacterium adolescent combined with cisplatin.Ratios of inhibitory activity on the growth of melanoma(B 16)were calculated.Pathology changes of the tumor were observed by HE staining.B 16 cell cycles were examined on a flow cytometer.Lymphocyte proliferation was measured with MTT assay and the T-cell subset was measured by double marked fluorescence.When bifidobacterium of 1010 cfu/L was injected,the ratio of inhibitory activity on the growth of melanoma(B16)reached 54%,which was similar to that of cisplatin group.The ratio of inhibitory activity reached 74.45% when the mice were treated by bifidobacterium combined with cisplatin,HE staining shows that bifidobacterium inhibited B16 cell proliferation and enhanced the cisplati(n)s killing activity on B16 cells.The results of flow cytometry demonstrated that B16 cell proliferation was arrested at G1 stage after treatment with bifidobacterium.The B16 cell proliferation was arrested at S stage after treatment with cisplatin.The CD4+ percentage increased and the difference was significant compared with the normal group after treatment with bifidobacterium,indicating that T-cell immune activity was enhanced.Treatment with bifidobacterium combined with cisplatin can enhance the inhibitory activity on the growth of melanoma(B16)of cisplatin.The mechanism of the inhibitory activity on B 16 cell proliferation is correlated with the enhanced immune activity in mice.

  11. Treatment of malignant melanoma by selective thermal neutron capture therapy using melanoma-seeking compound

    International Nuclear Information System (INIS)

    As pigment cells undergo melanoma genesis, accentuated melanogenesis concurrently occurs in principle. Subsequent to the understanding of intrinsic factors controlling both processes, we found our selective melanoma neutron capture therapy (NCT) using 10B-dopa (melanin substrate) analogue, 10B1-p-boronophenylalanine (10B1-BPA), followed by 10B(n, alpha)7Li reaction, induced by essentially harmless thermal neutrons, which releases energy of 2.33 MeV to 14 mu, the diameter of melanoma cells. In vitro/in vivo radiobiological analysis revealed the highly enhanced melanoma killing effect of 10B1-BPA. Chemical and prompt gamma ray spectrometry assays of 10B accumulated within melanoma cells after 10B1-BPA administration in vitro and in vivo show high affinity, e.g., 10B melanoma/blood ratio of 11.5. After successfully eradicating melanoma transplanted into hamsters with NCT, we advanced to preclinical studies using spontaneously occurring melanoma in Duroc pig skin. We cured three melanoma cases, 4.6 to 12 cm in diameter, by single neutron capture treatment. Complete disappearance of melanoma was obtained without substantial side effects. Acute and subacute toxicity as well as pharmacodynamics of 10B1-BPA have been studied in relation to therapeutic dosage requirements. Clinical radiation dosimetry using human phantom has been carried out. Further preclinical studies using human melanoma transplanted into nude mouse have been a useful model for obtaining optimal results for each melanoma type. We recently treated the first human melanoma patient with our NCT, using essentially the method for Duroc pig melanoma, and obtained similar regression time course leading to cure

  12. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2016-01-01

    of heritable melanoma risk genes is an important component of disease occurrence. Susceptibility for some families is due to mutation in one of the known high penetrance melanoma predisposition genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP and TERT. However, despite such mutations being implicated...

  13. Oral Melanoma

    Directory of Open Access Journals (Sweden)

    A Forouzandeh

    2002-02-01

    Full Text Available Melanoma is a malignant tumor that originates from melanocyte cells. Its oral type is rare. The goal of this investigation was to determine the prevalence of oral malignant melanoma in Iran, as determined by age, sex and location. This research reviewed 623 cases of oral and non-oral malignant melanoma in Immam-Khomeini hospital, Mearaj cancer institute and department of oral pathology of dental faculty, Tehran University of Medical Sciences in a period of 19 years from 1981-1999. The results showed that 54 cases of biopsy lesions were melanoma of oral cavity that included 7.8% of these lesions. The mean age incidence of oral melanoma was 55.5(between 26-86 years. The most prevalent sites were palate (37.1% and alveolar mucosa (20.4% and less common sites included floor of mouth. buccal mucosa and tongue.

  14. Role of SOCS-1 Gene on Melanoma Cell Growth and Tumor Development1

    OpenAIRE

    Scutti, Jorge A Borin; Matsuo, Alisson Leonardo; Pereira, Felipe Valença; Massaoka, Mariana Hiromi; Figueiredo, Carlos Rogério; Moreira, Dayson Friaça; Belizário, José Ernesto; Luiz R Travassos

    2011-01-01

    Melanoma is the most aggressive form of skin cancer, and its incidence has increased dramatically over the years. The murine B16F10 melanoma in syngeneic C57Bl/6 mice has been used as a highly aggressive model to investigate tumor development. Presently, we demonstrate in the B16F10-Nex2 subclone that silencing of SOCS-1, a negative regulator of Jak/Stat pathway, leads to reversal of the tumorigenic phenotype and inhibition of melanoma cell metastasis. SOCS-1 silencing with short hairpin RNA ...

  15. Polysaccharide from Inonotus obliquus inhibits migration and invasion in B16-F10 cells by suppressing MMP-2 and MMP-9 via downregulation of NF-κB signaling pathway.

    Science.gov (United States)

    Lee, Ki Rim; Lee, Jong Seok; Kim, Young Rae; Song, In Gyu; Hong, Eock Kee

    2014-05-01

    Polysaccharides derived from Inonotus obliquus (PIO) are known to possess multiple pharmacological activities including antitumor activity. However, the possible molecular mechanisms of these activities are unknown. In the present study, we determined the anti-metastatic potential and signaling pathways of PIO in the highly metastatic B16-F10 mouse melanoma cell line in vitro. We found that PIO suppressed the migration and invasive ability of B16-F10 cells and decreased the expression levels and activities of matrix metalloproteinase (MMP)-2 and MMP-9. In addition, PIO decreased the phosphorylation levels of extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK); PIO also decreased the expression level of cyclooxygenase (COX)‑2 and inhibited the nuclear translocation of nuclear factor κB (NF-κB) in B16-F10 melanoma cells. These results suggest that PIO could suppress the invasion and migration of B16-F10 melanoma cells by reducing the expression levels and activities of MMP-2 and MMP-9 through suppressing MAPK, COX-2 and NF-κB signaling pathways. PMID:24677090

  16. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

    Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

  17. Cutaneous melanoma

    International Nuclear Information System (INIS)

    The study of boron neutron capture therapy (BNCT) for malignant melanoma was initiated by Y. Mishima and his associates. Following basic research of 13 years, this team started the first clinical trial of cutaneous melanoma BNCT using 10B-para-boronophenylalanine (BPA) in 1985. Since then, 32 patients have been treated. We developed the following regimen for BNCT of malignant melanoma: 1) 170 - 250 mg/kg of BPA-fructose complex is administered by drip infusion over 3-hours. 2) The minimum dose for melanoma control by single irradiation is assumed to be 25 Gy-eq. 3) The maximum tolerable dose to the skin by single irradiation is assumed to be 18 Gy-eq. 4) As the therapeutic dose, the maximum tolerable dose to the skin itself is chosen. We report the clinical results of two patients with cutaneous melanoma treated by BNCT. We believe that cutaneous melanoma are suitable for BNCT and that the excellent results will have a great impact on patients in QOL. (author)

  18. The kin17 Protein in Murine Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Anelise C. Ramos

    2015-11-01

    Full Text Available kin17 has been described as a protein involved in the processes of DNA replication initiation, DNA recombination, and DNA repair. kin17 has been studied as a potential molecular marker of breast cancer. This work reports the detection and localization of this protein in the murine melanoma cell line B16F10-Nex2 and in two derived subclones with different metastatic potential, B16-8HR and B16-10CR. Nuclear and chromatin-associated protein fractions were analyzed, and kin17 was detected in all fractions, with an elevated concentration observed in the chromatin-associated fraction of the clone with low metastatic potential, suggesting that the kin17 expression level could be a marker of melanoma.

  19. The chemotherapeutic effect of essential oil of Plectranthus amboinicus (Lour) on lung metastasis developed by B16F-10 cell line in C57BL/6 mice.

    Science.gov (United States)

    Manjamalai, A; Grace, V M Berlin

    2013-01-01

    Current investigation is to evaluate the anticancer activity of the essential oil of Plectranthus amboinicus (Lour) on B16F-10 melanoma cell line injected C57BL/6 mice, and it was simultaneously treated with the essential oil of P. amboinicus (Lour) (50 μg/dose) via i.p. for 21 days. The present investigation exhibited the potent chemotherapeutic/chemopreventive effect of the essential oil of P. amboinicus (Lour) over lung metastasis that developed. To our knowledge, this is the first report in evaluating the effect of essential oil of P. amboinicus (Lour) using lung cancer model. PMID:23249189

  20. Bioelectric Applications for Treatment of Melanoma

    International Nuclear Information System (INIS)

    Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma

  1. Bioelectric Applications for Treatment of Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Beebe, Stephen J., E-mail: sbeebe@odu.edu; Schoenbach, Karl H.; Heller, Richard [Frank Reidy Research Center for Bioelectrics/Old Dominion University 4211 Monarch Way, Suite 300, Norfolk, Virginia 23508 (United States)

    2010-09-27

    Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma.

  2. Bioelectric Applications for Treatment of Melanoma

    Directory of Open Access Journals (Sweden)

    Richard Heller

    2010-09-01

    Full Text Available Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs. EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma.

  3. Melanoma Diagnosis

    Science.gov (United States)

    Horsch, Alexander

    The chapter deals with the diagnosis of the malignant melanoma of the skin. This aggressive type of cancer with steadily growing incidence in white populations can hundred percent be cured if it is detected in an early stage. Imaging techniques, in particular dermoscopy, have contributed significantly to improvement of diagnostic accuracy in clinical settings, achieving sensitivities for melanoma experts of beyond 95% at specificities of 90% and more. Automatic computer analysis of dermoscopy images has, in preliminary studies, achieved classification rates comparable to those of experts. However, the diagnosis of melanoma requires a lot of training and experience, and at the time being, average numbers of lesions excised per histology-proven melanoma are around 30, a number which clearly is too high. Further improvements in computer dermoscopy systems and their competent use in clinical settings certainly have the potential to support efforts of improving this situation. In the chapter, medical basics, current state of melanoma diagnosis, image analysis methods, commercial dermoscopy systems, evaluation of systems, and methods and future directions are presented.

  4. Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Eshini Perera

    2013-12-01

    Full Text Available Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns and improved rates of early diagnosis. Survival of melanoma has increased to over 90%. Management of melanoma involves a number of components: excision, tumor staging, re-excision with negative margins, adjuvant therapies (chemo, radiation or surgery, treatment of stage IV disease, follow-up examination for metastasis, lifestyle modification and counseling. Sentinel lymph node status is an important prognostic factor for survival in patients with a melanoma >1 mm. However, sentinel lymph node biopsies have received partial support due to the limited data regarding the survival advantage of complete lymph node dissection when a micrometastasis is detected in the lymph nodes. Functional mutations in the mitogen-activated pathways are commonly detected in melanomas and these influence the growth control. Therapies that target these pathways are rapidly emerging, and are being shown to increase survival rates in patients. Access to these newer agents can be gained by participation in clinical trials after referral to a multidisciplinary team for staging and re-excision of the scar.

  5. Elastin-derived peptides enhance melanoma growth in vivo by upregulating the activation of Mcol-A (MMP-1) collagenase

    OpenAIRE

    Devy, J; L. Duca; Cantarelli, B; Joseph-Pietras, D; Scandolera, A; Rusciani, A.; Parent, L.; Thevenard, J; Pasco, S Brassart; Tarpin, M; Martiny, L; Debelle, L

    2010-01-01

    Background: Elastin peptides possess several biological activities and in vitro data suggest they could be involved in the early phase of melanoma growth. Methods: Using diverse in vitro and in vivo techniques (cell proliferation, invasion and migration assays, zymography, western blots, collagen degradation assay, reverse transcription PCR, melanoma allographs and immunohistochemistry), we analysed the effect of elastin-derived peptides (EDPs) on B16F1 melanoma growth and invasion, as well a...

  6. Gallium-67-Labeled Lactam Bridge-Cyclized Alpha-Melanocyte Stimulating Hormone Peptide for Primary and Metastatic Melanoma Imaging

    OpenAIRE

    Guo, Haixun; Yang,Jianquan; Shenoy, Nalini; Miao, Yubin

    2009-01-01

    The purpose of this study was to examine the melanoma imaging properties of a novel 67Ga-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptide. A lactam bridge-cyclized α-MSH peptide, DOTA-GlyGlu-CycMSH {DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]}, was synthesized and radiolabeled with 67Ga. The melanoma targeting and pharmacokinetic properties of 67Ga-DOTA-GlyGlu-CycMSH were determined in B16/F1 flank primary melanoma-bearing and B16/F10 pu...

  7. The application of quantum dots for the melanoma tumor in vivo imaging

    Science.gov (United States)

    Feng, Yayi; Zhai, Peng; Wang, Xiaomei; Ying, Ming; Wu, Jinbo; Zhu, Xiaomei; Lin, Guimiao; Chen, Qiang; Xu, Gaixia

    2014-09-01

    Objective: Over the past decade, fluorescent semiconductor nanocrystals, also known as quantum dots (QDs), have been applied in biomedical imaging in vitro and in vivo because of their fascinating optical properties. In this work, we investigated the application of CdTe QDs for tumor fluorescence in vivo imaging. Methods: The transparent dorsal skin fold window chamber (DSFC) was constructed on the 4~6 week-old BALB/c mice. The melanoma cells stably expressing green fluorescent protein ---ZsGreen were transplanted into the chamber and the melanoma DSFC model was established successfully. The water soluble CdTe QDs were synthesized and then administrated in the model through the tail intravenous injection. The fluorescent expression of B16 cells were assayed by fluorescent microscopy, the tumor growth, the blood capillaries distributions and its dynamic changes were observed by stereomicroscopy and laser scanning confocal microscopy. Results: The results demonstrated that the expression efficiency of ZsGreen was 41%, which met the experimental requirement. The tumors was visible inside the chamber after implantation of melanoma cells for 5~6 days, while no obvious changes in mice behaviors were found. After injection of the QDs, CdTe QDs accumulated at the invading edge of a range of solid tumor. We could also observe the tumor cells growth near the blood vessels, the angiogenesis occurred inside the tumor and the local blood capillaries increased. Conclusions: This work provided a new strategy for the tumor in vivo imaging and the development of targeted antineoplastic drugs.

  8. Photodynamic therapy for melanoma: efficacy and immunologic effects

    Science.gov (United States)

    Avci, Pinar; Gupta, Gaurav K.; Kawakubo, Masayoshi; Hamblin, Michael R.

    2014-02-01

    Malignant melanoma is one of the fastest growing cancers and if it cannot be completely surgically removed the prognosis is bleak. Melanomas are known to be particularly resistant to both chemotherapy and radiotherapy. Various types of immunotherapy have however been investigated with mixed reports of success. Photodynamic therapy (PDT) has also been tested against melanoma, again with mixed effects as the melanin pigment is thought to act as both an optical shield and as an antioxidant. We have been investigating PDT against malignant melanoma in mouse models. We have compared B16F10 melanoma syngenic to C57BL/6 mice and S91 Cloudman melanoma syngenic to DBA2 mice. We have tested the hypothesis that S91 will respond better than B16 because of higher expression of immunocritical molecules such as MHC-1, tyrosinase, tyrosinase related protein-2 gp100, and intercellular adhesion molecule-1. Some of these molecules can act as tumor rejection antigens that can be recognized by antigen-specific cytotoxic CD8 T cells that have been stimulated by PDT. Moreover it is possible that DBA2 mice are intrinsically better able to mount an anti-tumor immune response than C57BL/6 mice. We are also studying intratumoral injection of photosensitzers such as benzoporphyrin monoacid ring A and comparing this route with the more usual route of intravenous administration.

  9. Comparing the efficacy of photodynamic and sonodynamic therapy in non-melanoma and melanoma skin cancer.

    Science.gov (United States)

    McEwan, Conor; Nesbitt, Heather; Nicholas, Dean; Kavanagh, Oisin N; McKenna, Kevin; Loan, Philip; Jack, Iain G; McHale, Anthony P; Callan, John F

    2016-07-01

    Sonodynamic therapy (SDT) involves the activation of a non-toxic sensitiser drug using low-intensity ultrasound to produce cytotoxic reactive oxygen species (ROS). Given the low tissue attenuation of ultrasound, SDT provides a significant benefit over the more established photodynamic therapy (PDT) as it enables activation of sensitisers at a greater depth within human tissue. In this manuscript, we compare the efficacy of aminolevulinic acid (ALA) mediated PDT and SDT in a squamous cell carcinoma (A431) cell line as well as the ability of these treatments to reduce the size of A431 ectopic tumours in mice. Similarly, the relative cytotoxic ability of Rose Bengal mediated PDT and SDT was investigated in a B16-melanoma cell line and also in a B16 ectopic tumour model. The results reveal no statistically significant difference in efficacy between ALA mediated PDT or SDT in the non-melanoma model while Rose Bengal mediated SDT was significantly more efficacious than PDT in the melanoma model. This difference in efficacy was, at least in part, attributed to the dark pigmentation of the melanoma cells that effectively filtered the excitation light preventing it from activating the sensitiser while the use of ultrasound circumvented this problem. These results suggest SDT may provide a better outcome than PDT when treating highly pigmented cancerous skin lesions. PMID:27234890

  10. Melanoma cells treated with GGTI and IFN-gamma allow murine vaccination and enhance cytotoxic response against human melanoma cells.

    Directory of Open Access Journals (Sweden)

    Guillaume Sarrabayrouse

    Full Text Available BACKGROUND: Suboptimal activation of T lymphocytes by melanoma cells is often due to the defective expression of class I major histocompatibility antigens (MHC-I and costimulatory molecules. We have previously shown that geranylgeranyl transferase inhibition (done with GGTI-298 stimulates anti-melanoma immune response through MHC-I and costimulatory molecule expression in the B16F10 murine model [1]. METHODOLOGY/PRINCIPAL FINDINGS: In this study, it is shown that vaccination with mIFN-gand GGTI-298 pretreated B16F10 cells induces a protection against untreated tumor growth and pulmonary metastases implantation. Furthermore, using a human melanoma model (LB1319-MEL, we demonstrated that in vitro treatment with hIFN-gamma and GGTI-298 led to the up regulation of MHC-I and a costimulatory molecule CD86 and down regulation of an inhibitory molecule PD-1L. Co-culture experiments with peripheral blood mononuclear cells (PBMC revealed that modifications induced by hIFN-gamma and GGTI-298 on the selected melanoma cells, enables the stimulation of lymphocytes from HLA compatible healthy donors. Indeed, as compared with untreated melanoma cells, pretreatment with hIFN-gamma and GGTI-298 together rendered the melanoma cells more efficient at inducing the: i activation of CD8 T lymphocytes (CD8+/CD69+; ii proliferation of tumor-specific CD8 T cells (MelanA-MART1/TCR+; iii secretion of hIFN-gamma; and iv anti-melanoma specific cytotoxic cells. CONCLUSIONS/SIGNIFICANCE: These data indicate that pharmacological treatment of melanoma cell lines with IFN-gamma and GGTI-298 stimulates their immunogenicity and could be a novel approach to produce tumor cells suitable for vaccination and for stimulation of anti-melanoma effector cells.

  11. Malignant Melanoma of the Foot

    Science.gov (United States)

    ... Text Size Print Bookmark Malignant Melanoma of the Foot What is Malignant Melanoma? Melanoma is a cancer ... age groups, even the young. Melanoma in the Foot Melanoma that occurs in the foot or ankle ...

  12. Development of radioiodine-labeled 4-hydroxyphenylcysteamine for specific diagnosis of malignant melanoma

    International Nuclear Information System (INIS)

    Introduction: A specific diagnosis for melanoma is strongly desired because malignant melanoma has poor prognosis. In a previous study, although radioiodine-125-labeled 4-hydroxyphenyl-L-cysteine (125I-L-PC) was found to have good substrate affinity for tyrosinase enzyme in the melanin metabolic pathway, 123/131I-L-PC had insufficient substrate affinity for tyrosinase to diagnose melanoma. In this study, we synthesized 4-hydroxyphenylcysteamine (4-PCA) and developed a novel radioiodine-125-labeled 4-hydroxyphenylcysteamine (125I-PCA) to increase affinity for the melanin biosynthesis pathway. Methods: 4-PCA was separated with 2-hydroxyphenylcysteamine (2-PCA), which is an isomer of 4-PCA, and was examined using melting point, proton nuclear magnetic resonance, mass spectrometry and elemental analysis. 125I-PCA was prepared using the chloramine-T method under no-carrier added conditions. We performed biodistribution experiments using B16 melanoma-bearing mice using 125I-PCA, 125I-L-PC, 125I-α-methyl-L-tyrosine, 123I-m-iodobenzylguanidine and 67Ga-citrate. In vitro assay was performed with B16 melanoma cells, and affinity for tyrosinase, DNA polymerase and amino acid transport was evaluated using phenylthiourea, thymidine, ouabine and L-tyrosine inhibitor. In addition, partition coefficients of 125I-PCA were evaluated. Results: In the synthesis of 4-PCA, analysis values did not differ between calculated and reported values, and 4-PCA was separated from 2-PCA at high purity. In biodistribution experiments, 125I-PCA was accumulated and retained in B16 melanoma cells when compared with 125I-L-PC. 125I-PCA showed the highest values at 60 min after radiotracer injection in melanoma-to-muscle ratios, melanoma-to-blood ratios and melanoma-to-skin ratios. Accumulation of 125I-PCA was significantly inhibited by phenylthiourea and thymidine. Partition coefficients of 125I-PCA were lower than those of N-isopropyl-p-[123I]iodoamphetamine and were not significantly different from

  13. Sinclair swine melanoma

    International Nuclear Information System (INIS)

    Sinclair(S-1) miniature swine spontaneously develop melanomas which have many biologic and histologic features in common with human superficial spreading melanoma. Host control of this neoplasm was indicated by the high incidence of spontaneous regression, a decrease in tumor development with age and a decrease in progressive growth of the tumor as age of tumor development increases. Immunologic mechanisms were implicated in host control by histologic observation of a mononuclear inflammatory infiltration of tumors which lead to depigmentation and fibrosis. In vitro immunologic studies revealed that leukocytes from melanoma swine were sensitized specifically to a tumor associated antigen like substance present in extracts of cutaneous melanomas and cultured swine melanoma cells and that melanoma swine leukocytes were cytotoxic for swine melanoma cells. Furthermore, these studies suggested the existence of a common cross reactive, melanoma associated antigen shared by human and swine melanomas. Antigenic analyses of swine melanomas with mouse monoclonal antibodies developed to a single swine melanoma cell culture and with rabbit antisera developed to pooled extracts of cutaneous melanomas demonstrated the presence of tumor associated antigens in swine melanoma cell culture and cutaneous melanomas. The failure of mouse monoclonal antibodies to detect antigens in cutaneous melanoma extracts and the failure of rabbit antisera to detect antigens in melanoma cell culture extracts suggested a differential in antigen expression between swine melanoma cells grown in vitro and in vivo

  14. Phosphatase of Regenerating Liver-3 Promotes Motility and Metastasis of Mouse Melanoma Cells

    OpenAIRE

    Wu, Xiaopeng; Zeng, Hu; Zhang, Xianming; Zhao, Ying; Sha, Haibo; Ge, Xiaomei; Zhang, Minyue; Gao, Xiang; Xu, Qiang

    2004-01-01

    Recent reports suggested that phosphatase of regenerating liver (PRL)-3 might be involved in colorectal carcinoma metastasis with an unknown mechanism. Here we demonstrated that PRL-3 expression was up-regulated in human liver carcinoma compared with normal liver. PRL-3 was also highly expressed in metastatic melanoma B16-BL6 cells but not in its lowly metastatic parental cell line, B16 cells. B16 cells transfected with PRL-3 cDNA displayed morphological transformation from epithelial-like sh...

  15. Choroidal melanoma

    International Nuclear Information System (INIS)

    A useful and practical guide is developed to better track to the uveal melanoma, due to its highly malignant character. Melanoma of the uveal tract (choroid, iris, ciliary body) has been the intraocular tumor most frequent in adults. The biopsy has been inaccessible, due to its location; therefore, the diagnostic should be based on clinical examination and the correct utilization of the diagnostic procedures (ultrasound, fluorescent angiography, computed axial tomography and magnetic resonance). The cases are diagnosed in the histological examination of the operatory piece post-enucleation for other causes. Epidemiological research has been key to determine the associated factors and better to understand the mechanisms of onset of the disease. Anatomopathological studies of choroidal melanoma have permitted to know the natural history of the disease. The decrease of the visual acuity, pain or inflammation are presented as a defect in the visual field. Different techniques to diagnose the disease are explained. Ultrasound in mode A and B, computed axial tomography and magnetic resonance are the diagnostic method of election. Ultrasound has been the primary method of diagnostic, giving the size and vascularisation, useful in tracking, when they are treated in shape conservatively, showing changes in echogenicity and less vascularisation as good response to treatment. The treatments of choroidal melanoma are specified. The correct interpretation of the clinical symptoms and early utilization of diagnostic imaging methods, have permitted to establish the adequate therapeutic and to avoid local and distant metastasis. The uveal melanoma, depending on their size and location, traditionally has been treated by enucleation. Data from the literature and authors, have promoted the conservation of the ocular globe, depending on the size of the tumor. Transpupillary thermotherapy has been an available alternative for small tumors in Costa Rica and level of social security

  16. Ethanolic Extract of Algerian Propolis and Galangin Decreased Murine Melanoma T.

    Science.gov (United States)

    Benguedouar, Lamia; Lahouel, Mesbah; Gangloff, Sophie C; Durlach, Anne; Grange, Florent; Bernard, Philippe; Antonicelli, Frank

    2016-01-01

    Melanoma is the more dangerous skin cancer, and metastatic melanoma still carries poor prognosis. Despite recent therapeutic advances, prolonged survival remains rare and research is still required. Propolis extracts from many countries have attracted a great deal of attention for their biological properties. We here investigated the ability of an ethanolic extract of Algerian propolis (EEP) to control melanoma tumour growth when given to mice bearing B16F1melanoma tumour either as preventive or as therapeutic treatment. EEP given after tumour occurrence increased mice survival (+30%) and reduced tumour growth (-75%). This was associated with a decrease of the Mitotic Index (-75%) and of Ki-67 (-50%) expression. When given either before or both before and after tumour occurrence, EEP reduced tumour growth but without prolonging mice life. Isolation of B16F1 melanoma cells from resected tumour showed that preventive and curative EEP treatments reduced invasiveness by 55% and 40% respectively compared to control. Galangin, one of the most abundant flavonoids in propolis, significantly reduced the number of melanoma cells in vitro and induced autophagy/apoptosis dose dependently. In conclusion, we showed that EEP reduced melanoma tumour progression/dissemination and could extend mice lifespan when used as therapeutic treatment. Then, EEP may help patients with melanoma when used as a complementary therapy to classical treatment for which autophagy is not contraindicated. PMID:26863880

  17. Transfer of the human sodium/iodide symporter gene enhances iodide uptake in melanoma cells

    International Nuclear Information System (INIS)

    Objective: To obtain human sodium/iodide symporter (hNIS) cDNA and to study its biological property and potential use as a therapeutic radioiodide for melanoma. Methods: hNIS gene cDNA was amplified with total RNA from human thyroid tissue by RT-PCR. The hNIS cDNA was inserted into cloning vector pUCm-T and subcloned into eukaryotic expression vector pcDNA3. The recombinant plasmid pcDNA3-hNIS was introduced into B16 cells using the electroporation technique. The uptake and efflux of iodide was examined in vitro. Results: The cloned hNIS cDNA sequence was identical to the published sequence. Two novel cell lines named B16-A containing hNIS and B16-B containing pcDNA3 only were established. The resultant cell line B16-A accumulated 17 and 19 times more radioiodide in vitro than B16 and B16-B did, respectively. However the efflux of iodide from B16-A was also rapid ( T1/2=10 min). Conclusions: Our preliminary data indicate that the transduction of the hNIS gene per se is sufficient to induce iodide transport in melanoma cells in vitro, but its T1/2 is short. With regard to therapeutic application, however, further investigation is necessary so as to develop a method of maintaining more radioiodide in the cells for long enough to produce greater therapeutic effects

  18. Stages of Melanoma

    Science.gov (United States)

    ... melanoma cells. The disease is metastatic melanoma, not lung cancer. The method used to stage melanoma is based mainly on the thickness of the tumor and whether cancer has spread to lymph nodes or other parts of the body. The staging of melanoma depends on the following: The thickness ...

  19. Liposomal encapsulation enhances the antitumour efficacy of the vascular disrupting agent ZD6126 in murine B16.F10 melanoma

    OpenAIRE

    Fens, M H A M; Hill, K. J.; Issa, J; Ashton, S E; Westwood, F. R.; Blakey, D C; Storm, G; Ryan, A J; Schiffelers, R.M.

    2008-01-01

    Vascular disrupting agents (VDAs) are able to affect selectively tumour endothelial cell morphology resulting in vessel occlusion and widespread tumour cell necrosis. However, single-agent antitumour activity of VDAs is typically limited, as tumour regrowth occurs rapidly following drug treatment. To improve the therapeutic effectiveness of VDAs, we investigated liposomal targeting using ZD6126 as a model VDA. ZD6126 is a phosphate-prodrug of the tubulin-binding vascular disrupting agent ZD61...

  20. Cinnamomum cassia Essential Oil Inhibits α-MSH-Induced Melanin Production and Oxidative Stress in Murine B16 Melanoma Cells

    OpenAIRE

    Ying Shih; Shih-Lan Hsu; Yu-Che Lin; Chen-Tien Chang; Su-Tze Chou; Wen-Lun Chang

    2013-01-01

    Essential oils extracted from aromatic plants exhibit important biological activities and have become increasingly important for the development of aromatherapy for complementary and alternative medicine. The essential oil extracted from Cinnamomum cassia Presl (CC-EO) has various functional properties; however, little information is available regarding its anti-tyrosinase and anti-melanogenic activities. In this study, 16 compounds in the CC-EO have been identified; the major components of t...

  1. Inhibitory and Acceleratory Effects of Inonotus obliquus on Tyrosinase Activity and Melanin Formation in B16 Melanoma Cells

    OpenAIRE

    Zheng-Fei Yan; Yang Yang; Feng-Hua Tian; Xin-Xin Mao; Yu Li; Chang-Tian Li

    2014-01-01

    The aim of the present study is to preliminarily investigate the antimelanogenesis effect of Inonotus obliquus extracts by cell-free mushroom tyrosinase assay. It was found that petroleum ether and n-butanol extracts might contain unknown potential tyrosinase inhibitors, while its ethyl acetate extract might contain some unknown accelerators. Six compounds were isolated and their structures were identified by interpretation of NMR data and nicotinic acid was first discovered in Inonotus obliq...

  2. Inhibitory and Acceleratory Effects of Inonotus obliquus on Tyrosinase Activity and Melanin Formation in B16 Melanoma Cells.

    Science.gov (United States)

    Yan, Zheng-Fei; Yang, Yang; Tian, Feng-Hua; Mao, Xin-Xin; Li, Yu; Li, Chang-Tian

    2014-01-01

    The aim of the present study is to preliminarily investigate the antimelanogenesis effect of Inonotus obliquus extracts by cell-free mushroom tyrosinase assay. It was found that petroleum ether and n-butanol extracts might contain unknown potential tyrosinase inhibitors, while its ethyl acetate extract might contain some unknown accelerators. Six compounds were isolated and their structures were identified by interpretation of NMR data and nicotinic acid was first discovered in Inonotus obliquus. In cells testing, betulin and trametenolic acid decreased tyrosinase activity and melanin content, while inotodiol and lanosterol significantly increased tyrosinase activity and melanin content, showing an AC⁡50 of 9.74 and 8.43 μM, respectively. Nicotinie acid, 3β,22,25-trihydroxy-lanosta-8-ene, had a little or no effect on tyrosinase. Betulin exhibited a mode of noncompetitive inhibition with a K I = K IS of 0.4 μM on tyrosinase activity showing an IC50 of 5.13 μM and being more effective than kojic acid (6.43 μM), and trametenolic acid exhibited a mode of mixed inhibition with a K I of 0.9 μM, K IS of 0.5 μM, and an IC50 of 7.25 μM. We proposed betulin and trametenolic acid as a new candidate of potent tyrosinase inhibitors and inotodiol and lanosterol as accelerators that could be used as therapeutic agent. PMID:25197307

  3. Suppressive Effect of Juzen-Taiho-To on Lung Metastasis of B16 Melanoma Cells In Vivo

    OpenAIRE

    Takako Matsuda; Katsuhiko Maekawa; Kazuhito Asano; Tadashi Hisamitsu

    2011-01-01

    Juzen-Taiho-To (JTT) is well known to be one of Kampo (Japanese herbal) medicine consisted of 10 component herbs and used for the supplemental therapy of cancer patients with remarkably success. However, the precise mechanisms by which JTT could favorably modify the clinical conditions of cancer patients are not well defined. The present study, therefore, was undertaken to examine the possible mechanisms of JTT on prevention of cancer metastasis using experimental mouse model. JTT was well mi...

  4. Inhibitory and Acceleratory Effects of Inonotus obliquus on Tyrosinase Activity and Melanin Formation in B16 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Zheng-Fei Yan

    2014-01-01

    Full Text Available The aim of the present study is to preliminarily investigate the antimelanogenesis effect of Inonotus obliquus extracts by cell-free mushroom tyrosinase assay. It was found that petroleum ether and n-butanol extracts might contain unknown potential tyrosinase inhibitors, while its ethyl acetate extract might contain some unknown accelerators. Six compounds were isolated and their structures were identified by interpretation of NMR data and nicotinic acid was first discovered in Inonotus obliquus. In cells testing, betulin and trametenolic acid decreased tyrosinase activity and melanin content, while inotodiol and lanosterol significantly increased tyrosinase activity and melanin content, showing an AC⁡50 of 9.74 and 8.43 μM, respectively. Nicotinie acid, 3β,22,25-trihydroxy-lanosta-8-ene, had a little or no effect on tyrosinase. Betulin exhibited a mode of noncompetitive inhibition with a KI=KIS of 0.4 μM on tyrosinase activity showing an IC50 of 5.13 μM and being more effective than kojic acid (6.43 μM, and trametenolic acid exhibited a mode of mixed inhibition with a KI of 0.9 μM, KIS of 0.5 μM, and an IC50 of 7.25 μM. We proposed betulin and trametenolic acid as a new candidate of potent tyrosinase inhibitors and inotodiol and lanosterol as accelerators that could be used as therapeutic agent.

  5. Subphthalocyanines: addressing water-solubility, nano-encapsulation, and activation for optical imaging of B16 melanoma cells.

    Science.gov (United States)

    Bernhard, Yann; Winckler, Pascale; Chassagnon, Remi; Richard, Philippe; Gigot, Élodie; Perrier-Cornet, Jean-Marie; Decréau, Richard A

    2014-11-21

    Water-soluble disulfonato-subphthalocyanines (SubPcs) or hydrophobic nano-encapsulated SubPcs are efficient probes for the fluorescence imaging of cells. 20 nm large liposomes (TEM and DLS) incorporated about 13% SubPc. Moreover, some of these fluorophores were found to be pH activatable. PMID:25266256

  6. Improving anticancer efficacy of (-)-epigallocatechin-3-gallate gold nanoparticles in murine B16F10 melanoma cells

    OpenAIRE

    Yeh, Ming-kung

    2014-01-01

    Cheng-Cheung Chen,1,2 Dar-Shih Hsieh,1,3 Kao-Jean Huang,4 Yi-Lin Chan,5 Po-Da Hong,6 Ming-Kung Yeh,6–8,* Chang-Jer Wu1,*1Department of Food Science, National Taiwan Ocean University, Keelung, 2Institute of Preventive Medicine, National Defense Medical Center, Taipei, 3Division of Urology, Department of Surgery, Ren-Ai Hospital, Shulin, New Taipei City, 4Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, 5Graduate Institute of Medical Sc...

  7. Improving anticancer efficacy of (-)-epigallocatechin-3-gallate gold nanoparticles in murine B16F10 melanoma cells

    OpenAIRE

    Chen CC; Hsieh DS; Huang KJ; Chan YL; Hong PD; Yeh MK; Wu CJ

    2014-01-01

    Cheng-Cheung Chen,1,2 Dar-Shih Hsieh,1,3 Kao-Jean Huang,4 Yi-Lin Chan,5 Po-Da Hong,6 Ming-Kung Yeh,6–8,* Chang-Jer Wu1,*1Department of Food Science, National Taiwan Ocean University, Keelung, 2Institute of Preventive Medicine, National Defense Medical Center, Taipei, 3Division of Urology, Department of Surgery, Ren-Ai Hospital, Shulin, New Taipei City, 4Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, 5Graduate Institute of Medical Scienc...

  8. Recombinant Interferon Alfa-2b in Treating Patients With Melanoma

    Science.gov (United States)

    2016-05-17

    Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  9. Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

    International Nuclear Information System (INIS)

    Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. B16 (mouse melanoma) and C6 (rat glioma) cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet p53 was further activated by the combination of p19

  10. Establishment and characterization of human uveal malignant melanoma xenografts in nude mice

    DEFF Research Database (Denmark)

    Heegaard, S; Spang-Thomsen, M; Prause, J U

    2003-01-01

    model. Tumour tissue blocks (2 x 2 x 2 mm) from enucleated eyes with choroidal malignant melanoma were transplanted subcutaneously into the flanks of nude mice. The growing tumours were measured and serially transplanted. The tumour samples were investigated by histology, immunohistochemistry and......The purpose of this study was to develop a suitable animal model for the investigation of the pathogenesis and therapy of uveal malignant melanoma. Eight choroidal malignant melanomas from eight patients were transplanted into nude mice in an attempt to establish a serially transplantable tumour...... electron microscopy. Only one of the eight transplanted primary tumours (13%) was established as a xenograft in nude mice. Furthermore, the take rate of the transplantable tumour was low (13%). The growth of the tumour fitted a Gompertz function, and the calculated tumour volume doubling time was 54 days...

  11. Cripto-1 vaccination elicits protective immunity against metastatic melanoma

    Science.gov (United States)

    Ligtenberg, M. A.; Witt, K.; Galvez-Cancino, F.; Sette, A.; Lundqvist, A.; Lladser, A.; Kiessling, R.

    2016-01-01

    ABSTRACT Metastatic melanoma is a fatal disease that responds poorly to classical treatments but can be targeted by T cell-based immunotherapy. Cancer vaccines have the potential to generate long-lasting cytotoxic CD8+ T cell responses able to eradicate established and disseminated tumors. Vaccination against antigens expressed by tumor cells with enhanced metastatic potential represents a highly attractive strategy to efficiently target deadly metastatic disease. Cripto-1 is frequently over-expressed in human carcinomas and melanomas, but is expressed only at low levels on normal differentiated tissues. Cripto-1 is particularly upregulated in cancer-initiating cells and is involved in cellular processes such as cell migration, invasion and epithelial–mesenchymal transition, which are hallmarks of aggressive cancer cells able to initiate metastatic disease. Here, we explored the potential of Cripto-1 vaccination to target metastatic melanoma in a preclinical model. Cripto-1 was overexpressed in highly metastatic B16F10 cells as compared to poorly metastatic B16F1 cells. Moreover, B16F10 cells grown in sphere conditions to enrich for cancer stem cells (CSC) progressively upregulated cripto1 expression. Vaccination of C57Bl/6 mice with a DNA vaccine encoding mouse Cripto-1 elicited a readily detectable/strong cytotoxic CD8+ T cell response specific for a H-2 Kb-restricted epitope identified based on its ability to bind H-2b molecules. Remarkably, Cripto-1 vaccination elicited a protective response against lung metastasis and subcutaneous challenges with highly metastatic B16F10 melanoma cells. Our data indicate that vaccination against Cripto-1 represents a novel strategy to be tested in the clinic.

  12. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome

    International Nuclear Information System (INIS)

    The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β and IL-18 secretion. The NLRP3 (NACHT, LRR, and pyrin domain-containing protein 3) inflammasome is constitutively assembled and activated in human melanoma cells. We have examined the inhibitory effect of thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone), a major ingredient of black seed obtained from the plant Nigella sativa on metastatic human (A375) and mouse (B16F10) melanoma cell lines. We have assessed whether thymoquinone inhibits metastasis of melanoma cells by targeting NLRP3 subunit of inflammasomes. Using an in vitro cell migration assay, we found that thymoquinone inhibited the migration of both human and mouse melanoma cells. The inhibitory effect of thymoquinone on metastasis was also observed in vivo in B16F10 mouse melanoma model. The inhibition of migration of melanoma cells by thymoquinone was accompanied by a decrease in expression of NLRP3 inflammasome resulting in decrease in proteolytic cleavage of caspase-1. Inactivation of caspase-1 by thymoquinone resulted in inhibition of IL-1β and IL-18. Treatment of mouse melanoma cells with thymoquinone also inhibited NF-κB activity. Furthermore, inhibition of reactive oxygen species (ROS) by thymoquinone resulted in partial inactivation of NLRP3 inflammasome. Thus, thymoquinone exerts its inhibitory effect on migration of human and mouse melanoma cells by inhibition of NLRP3 inflammasome. Thus, our results indicate that thymoquinone can be a potential immunotherapeutic agent not only as an adjuvant therapy for melanoma, but also, in the control and prevention of metastatic melanoma. - Highlights: • Thymoquinone causes inhibition of migration of melanoma cells. • Thymoquinone causes inhibition of metastasis in vivo. • Thymoquinone causes inhibition of migration by activation of NLRP3 inflammasome

  13. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Israr; Muneer, Kashiff M.; Tamimi, Iman A.; Chang, Michelle E.; Ata, Muhammad O. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, AL (United States); Yusuf, Nabiha, E-mail: nabiha@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, AL (United States); Veteran Affairs Medical Center, Birmingham, University of Alabama at Birmingham, AL (United States); Comprehensive Cancer Center, University of Alabama at Birmingham, AL (United States)

    2013-07-01

    The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β and IL-18 secretion. The NLRP3 (NACHT, LRR, and pyrin domain-containing protein 3) inflammasome is constitutively assembled and activated in human melanoma cells. We have examined the inhibitory effect of thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone), a major ingredient of black seed obtained from the plant Nigella sativa on metastatic human (A375) and mouse (B16F10) melanoma cell lines. We have assessed whether thymoquinone inhibits metastasis of melanoma cells by targeting NLRP3 subunit of inflammasomes. Using an in vitro cell migration assay, we found that thymoquinone inhibited the migration of both human and mouse melanoma cells. The inhibitory effect of thymoquinone on metastasis was also observed in vivo in B16F10 mouse melanoma model. The inhibition of migration of melanoma cells by thymoquinone was accompanied by a decrease in expression of NLRP3 inflammasome resulting in decrease in proteolytic cleavage of caspase-1. Inactivation of caspase-1 by thymoquinone resulted in inhibition of IL-1β and IL-18. Treatment of mouse melanoma cells with thymoquinone also inhibited NF-κB activity. Furthermore, inhibition of reactive oxygen species (ROS) by thymoquinone resulted in partial inactivation of NLRP3 inflammasome. Thus, thymoquinone exerts its inhibitory effect on migration of human and mouse melanoma cells by inhibition of NLRP3 inflammasome. Thus, our results indicate that thymoquinone can be a potential immunotherapeutic agent not only as an adjuvant therapy for melanoma, but also, in the control and prevention of metastatic melanoma. - Highlights: • Thymoquinone causes inhibition of migration of melanoma cells. • Thymoquinone causes inhibition of metastasis in vivo. • Thymoquinone causes inhibition of migration by activation of NLRP3 inflammasome.

  14. What Is Melanoma Skin Cancer?

    Science.gov (United States)

    ... statistics for melanoma skin cancer What is melanoma skin cancer? Cancer starts when cells in the body begin ... causing the skin to tan or darken. Melanoma skin cancers Melanoma is a cancer that begins in the ...

  15. Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue

    DEFF Research Database (Denmark)

    Schrama, D.; Voigt, H.; Eggert, A.O.;

    2008-01-01

    BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune...

  16. Notch ligand Delta-like 1 promotes the metastasis of melanoma by enhancing tumor adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, J.P. [Department of Orthopedic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi' an (China); Li, N. [Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi' an (China); Bai, W.Z.; Qiu, X.C.; Ma, B.A.; Zhou, Y.; Fan, Q.Y.; Shan, L.Q. [Department of Orthopedic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi' an (China)

    2014-03-28

    Notch signaling plays a vital role in tumorigenicity and tumor progression by regulating proliferation, invasion, and the tumor microenvironment. Previous research by our group indicated that Notch ligand Delta-like 1 (Dll1) is involved in angiogenesis in melanoma, and we noticed that it took a longer time to trypsinize Dll1-expressing B16 melanoma cells than the control cells. In this article, we extended our study to investigate the effects of Dll1 on tumor cell adhesion and metastasis. Dll1 overexpression activated Notch signaling in B16 tumor cells and significantly enhanced the adhering capacity of B16 tumor cells both in vitro and in vivo. B16-Dll1 cells also had a higher metastatic potential than their counterpart in the mouse model of lung metastasis. Along with increased Dll1 expression, N-cadherin, but not E-cadherin, was upregulated in B16-Dll1 cells. These data suggested that Notch ligand Dll1 may enhance the adhesion and metastasis of melanoma cells by upregulation of N-cadherin.

  17. Notch ligand Delta-like 1 promotes the metastasis of melanoma by enhancing tumor adhesion

    International Nuclear Information System (INIS)

    Notch signaling plays a vital role in tumorigenicity and tumor progression by regulating proliferation, invasion, and the tumor microenvironment. Previous research by our group indicated that Notch ligand Delta-like 1 (Dll1) is involved in angiogenesis in melanoma, and we noticed that it took a longer time to trypsinize Dll1-expressing B16 melanoma cells than the control cells. In this article, we extended our study to investigate the effects of Dll1 on tumor cell adhesion and metastasis. Dll1 overexpression activated Notch signaling in B16 tumor cells and significantly enhanced the adhering capacity of B16 tumor cells both in vitro and in vivo. B16-Dll1 cells also had a higher metastatic potential than their counterpart in the mouse model of lung metastasis. Along with increased Dll1 expression, N-cadherin, but not E-cadherin, was upregulated in B16-Dll1 cells. These data suggested that Notch ligand Dll1 may enhance the adhesion and metastasis of melanoma cells by upregulation of N-cadherin

  18. Improved anti-melanoma effect of a transdermal mitoxantrone ethosome gel.

    Science.gov (United States)

    Yu, Xiang; Du, Lina; Li, Yu; Fu, Guiying; Jin, Yiguang

    2015-07-01

    Melanomas are malignant tumors characterized by early metastasis, rapid development, poor prognosis and high mortality. A highly effective and convenient method is necessary for long-term treatment of melanomas. Mitoxantrone (MTO) was topically applied for melanoma therapy using an MTO ethosome gel. Firstly, an ethosome was prepared from MTO, phospholipids, ethanol and water followed by addition of hydroxypropyl methylcellulose to obtain an ethosome gel. The ethosome was characterized. The cytotoxicity on B16 melanoma cells was evaluated on an electrical cell-substrate impedance sensing system with a novel modified chip. In vivo anti-melanoma effect of the ethosome gel was explored. Immunohistochemical and flow cytometric investigations were done. The MTO ethosomes had the size of 78nm and the zeta potential of -55mV. The ethosomes were flexible vesicles and showed much higher in vitro permeability across the rat skin than MTO aqueous solutions. The ethosomes had significant cytotoxicity and higher in vivo anti-melanoma effect than MTO solutions. The calreticulin membrane translocation of B16 cells was improved by the MTO ethosomes and the cell uptake of MTO was confirmed. The MTO ethosome gel is a promising transdermal delivery system for melanoma therapy with the advantages of non-invasion and no significant side effects. PMID:26211575

  19. Radioiodide uptake in melanoma cells after transfer of human NaI symporter gene

    International Nuclear Information System (INIS)

    To obtain human sodium/iodide symporter gene cDNA for studying its potential ability as a radioiodide treatment for melanoma, the hNIS gene cDNA was amplified with total RNA from human thyroid tissue by RT-PCR. The hNIS cDNA was inserted into cloning vector pUCm-T and subcloned into eukaryotic expression vector pc-DNA3. The pc-DNA3-hNIS and pc-DNA3 were transduced into melanoma cells (B16) by electroporation, and two cell lines termed B16-A and B16-B respectively were established. The uptake and efflux of iodide was examined in vitro. The three cell lines (B16-A, B16-B, B16) were injected subcutaneously into the right flank of C57 mice. Biodistribution study and tumor imaging were performed when the tumor reached approximately 10 mm in diameter. The cloned hNIS cDNA sequence was identical with the published sequence. Two novel cell lines named B16-A containing pc-DNA3-hNIS and B16-B containing pc-DNA3 only were established. The resultant cell line B16-A accumulated 17 and 19 times more radioiodide in vitro than B16 and B16-B respectively. The iodide uptake reached the half-maximal level within 10 min, and reached a plateau at 30 min. The efflux of iodide was also rapid (T1/2eff=10 min). The imaging shows in vivo uptake in expected sites including the salivary glands, thyroid, stomach, and hNIS-transduced tumor, whereas the nontransduced tumor was not visualized. The %ID/g of B16-A tumors at 1,2,4,12 and 24h after injection of 125I were 12.22 ± 0.71, 10.91 ± 0.72, 8.73 ± 0.99, 1.24 ± 0.29, and 0.19 ± 0.03, respectively, which were significantly higher percentages than those for controlling tumors, p1/2 was about 6 h. Our preliminary data indicate that the transduction of the hNIS gene per se is sufficient to induce iodide transport in melanoma cells both in vitro and in vivo, but T1/2eff is short. (authors)

  20. Estudio tribológico comparativo de los Babbits Fórmula V y B-16 // Babbits comparative Study About Fórmulas V and B-16

    Directory of Open Access Journals (Sweden)

    M. Díaz Díaz

    1999-01-01

    Full Text Available En el trabajo se realiza un estudio comparativo del coeficiente de fricción de los Babbits, fórmula V y B-16, así como lainfluencia que ejerce sobre estos la presión de trabajo y el ángulo de contacto entre el cojinete y el árbol, determinándose lasexpresiones empíricas que rigen esta relación para ambos materiales antifricción.Palabras claves: Babbi t s, presión, angulo de contacto, coj inetes de desl izamiento._________________________________________________________________________________AbstractIn this work is made a comparative study about the friction coefficients of Babbits metals, Fórmula V and B-16, taking intoaccost influence the pressure and contact angle between shaft and bearing. Empirical relations for both antifriction materials aregiven.Key words: Babbi t s, pressure, contact angle, plain bearings

  1. Inhibitory Effect of Doxycycline on the Adhesion of Melanoma Cells and Its MolecularMechanisms%多西环素抑制黑色素瘤细胞黏附的分子机制研究

    Institute of Scientific and Technical Information of China (English)

    董恒磊; 孙保存; 孙涛; 赵楠; 董学易; 车娜; 赵秀兰

    2011-01-01

    Objective: To investigate the inhibitory effect of Doxycycline on the adhesion of melanoma cells and its mechanism.Methods: Melanoma B16F110, WM351 and WM451 cell lines were treated with Doxycycline at different doses and through different administration methods.MMT, cell adhesion experiment and Western blot were used to observe the effect of different treatment.A total of 20 C57/BL mice were transplanted with melanoma through injection of B16F10 cells and were divided into two groups.One group was treated with Doxycycline, and the other NaCl solution.Carcinoma tissues were obtained and underwentWestern blot and gelatin zymography.Results: MTT analysis showed that the inhibition ratio was significantly higher in the group receiving treatment before cell adhesion than in the group receiving treatment after cell adhesion ( P < 0.05 ).Cell adhesion experiment showed that Doxycycline had an inhibitory effect on the adhesion of B16F110, WM351 and WM451 cells, with a statistical significance ( P < 0.05 ).Western blot revealed that FAK expression in the three cell lines was decreased at 12 h after Doxycycline treatment.Observations from the mice melanoma model suggested obvious changes in FAK expression and its phosphorylation level ( P < 0.05 ).Conclusion: Doxycycline can interfere the adhesion of melanoma cells, possibly through inhibiting FAK expression and its phosphorylation.%目的:研究多西环素对黑色素瘤细胞黏附的抑制作用及分子机制.方法:对黑色素瘤细胞系B16F10、WM351、WM451分别以不同给药方式和给药浓度进行处理,利用MTT实验、细胞黏附实验和Western blot技术检测比较其差异.C57/BL小鼠20只进行黑色素瘤动物实验,接种B16F10后随机分为2组,分别给予多西环素和NaCl溶液处理,取瘤组织进行Western blot和明胶酶谱检测.结果:MTT实验显示"贴壁前"给药组的细胞抑制率显著高于"贴壁后"给药组且差异具有统计学意义(P<0.05).细胞黏附实

  2. The leaf extract of Mallotus japonicus and its major active constituent, rutin,suppressed on melanin production in murine B16F1 melanoma简

    Institute of Scientific and Technical Information of China (English)

    Junsei; Taira; Eito; Tsuchida; Masatsugu; Uehara; Natsuko; Ohhama; Wakana; Ohmine; Takayuki; Ogi

    2015-01-01

    Objective: To find anti-melanogenesis materials used in whitening cosmetics.Methods: The ethanolic leaf extract of Mallotus japonicus(M. japonicus) having an anti-melanogenesis activity was separated by a sephadex LH-20 chromatography. Each fraction was measured for its tyrosinase inhibitory activity together with its polyphenol content using the Folin–Ciocalteu method. The anti-melanogenesis activity of the active fractions was determined by the melanin content in the murine B16F1 melanoma. The active fractions were put together due to similar constituents, and then separated by high performance liquid chromatography using a C-18 ODS column. The major antimelanogenesis compound was identified using1 H and13C-NMR and liquid chromatography-mass spectrometry.Results: The ethanolic leaf extract of M. japonicus showed an anti-tyrosinase activity with a high polyphenol content, resulting in suppression of melanin production in the B16F1 melanoma. The extract was separated and the active compound was identical as rutin based on the1 H,13C-NMR and liquid chromatography-mass spectrometry analysis data. In addition, the rutin treatment with cells reduced the melanin content in a concentration dependent manner without any cell toxicity. The leaf extract of M. japonicus containing rutin would be useful in whitening cosmetics for protection from UV-light exposure to be limiting the accumulation of melanin in skin.Conclusions: The leaf extract of M. japonicus and/or rutin isolated from the extract as a key whitening agent would be useful as a whitening cosmetic material for protecting against disorder skin due to melanin accumulation.

  3. Melanoma Cell Expression of CD200 Inhibits Tumor Formation and Lung Metastasis via Inhibition of Myeloid Cell Functions

    OpenAIRE

    Talebian, Fatemeh; Liu, Jin-Qing; Liu, Zhenzhen; Khattabi, Mazin; He, Yukai; Ganju, Ramesh; Bai, Xue-feng

    2012-01-01

    CD200 is a cell surface glycoprotein that functions through engaging CD200 receptor on cells of the myeloid lineage and inhibits their functions. Expression of CD200 has been implicated in a variety of human cancer cells including melanoma cells and has been thought to play a protumor role. To investigate the role of cancer cell expression of CD200 in tumor formation and metastasis, we generated CD200-positive and CD200-negative B16 melanoma cells. Subcutaneous injection of CD200-positive B16...

  4. Transplant Considerations

    Science.gov (United States)

    ... to 20-year friendship Supporter stories Valerie Sun - bone marrow transplant patient advocate Jeff and Kim take their life- ... transplant and other treatment options What is a bone marrow transplant How a bone marrow transplant works Transplant process ...

  5. Nanodiamonds coupled with 5,7-dimethoxycoumarin, a plant bioactive metabolite, interfere with the mitotic process in B16F10 cells altering the actin organization

    Directory of Open Access Journals (Sweden)

    Gismondi A

    2016-02-01

    Full Text Available Angelo Gismondi,1 Valentina Nanni,1 Giacomo Reina,2 Silvia Orlanducci,2 Maria Letizia Terranova,2 Antonella Canini1 1Department of Biology, 2Department of Chemical Science and Technology, University of Rome “Tor Vergata”, Rome, Italy Abstract: For the first time, we coupled reduced detonation nanodiamonds (NDs with a plant secondary metabolite, citropten (5,7-dimethoxycoumarin, and demonstrated how this complex was able to reduce B16F10 tumor cell growth more effectively than treatment with the pure molecule. These results encouraged us to find out the specific mechanism underlying this phenomenon. Internalization kinetics and quantification of citropten in cells after treatment with its pure or ND-conjugated form were measured, and it was revealed that the coupling between NDs and citropten was essential for the biological properties of the complex. We showed that the adduct was not able to induce apoptosis, senescence, or differentiation, but it determined cell cycle arrest, morphological changes, and alteration of mRNA levels of the cytoskeletal-related genes. The identification of metaphasic nuclei and irregular disposition of β-actin in the cell cytoplasm supported the hypothesis that citropten conjugated with NDs showed antimitotic properties in B16F10 cells. This work can be considered a pioneering piece of research that could promote and support the biomedical use of plant drug-functionalized NDs in cancer therapy. Keywords: citropten, cytoskeletal structure, plant secondary metabolite, melanoma, internalization kinetics

  6. Imaging malignant melanoma with {sup 18}F-5-FPN

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Hongyan; Xia, Xiaotian; Li, Chongjiao; Song, Yiling; Qin, Chunxia; Liu, Qingyao; Zhang, Yongxue; Lan, Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (China); Hubei Key Laboratory of Molecular Imaging (China)

    2016-01-15

    Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. {sup 18}F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide ({sup 18}F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma. {sup 18}F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using {sup 18}F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with {sup 18}F-FDG. PET imaging with {sup 18}F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases. {sup 18}F-5-FPN was successfully prepared with radiochemical yields of 5 - 10 %. Binding of {sup 18}F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. {sup 18}F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 ± 6.32 %ID/g and 16.63 ± 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. {sup 18}F-5-FPN and {sup 18}F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of {sup 18}F-5-FPN was ten times higher than that of {sup 18}F-FDG (35.22 ± 7.02 vs. 3.29 ± 0.53, five mice). {sup 18}F-5-FPN PET imaging also detected simulated lung metastases measuring 1 - 2 mm. {sup 18}F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity

  7. Effect of homeopathic medicines on transplanted tumors in mice.

    Science.gov (United States)

    Es, Sunila; Kuttan, Girija; Kc, Preethi; Kuttan, Ramadasan

    2007-01-01

    Ultra low doses used in homeopathic medicines are reported to have healing potential for various diseases but their action remains controversial. In this study we have investigated the antitumour and antimetastatic activity of selected homeopathic medicines against transplanted tumours in mice. It was found that Ruta graveolens 200c and Hydrastis canadensis 200c significantly increased the lifespan of Ehrlich Ascites Carcinoma and Dalton's Lymphoma Ascites induced tumour-bearing animals by 49.7%, and 69.4% respectively. Moreover there was 95.6% and 95.8% reduction of solid tumour volume in Ruta 200c and Hydrastis 200c treated animals on the 31st day after tumour inoculation. Hydrastis 1M given orally significantly inhibited the growth of developed solid tumours produced by DLA cells and increased the lifespan of tumour bearing animals. Some 9 out of 15 animals with developed tumors were completely tumour free after treatment with Hydrastis 1M. Significant anti-metastatic activity was also found in B16F-10 melanoma-bearing animals treated with Thuja1M, Hydrastis 1M and Lycopodium1M. This was evident from the inhibition of lung tumour nodule formation, morphological and histopathological analysis of lung and decreased levels of gamma-GT in serum, a cellular marker of proliferation. These findings support that homeopathic preparations of Ruta and Hydrastis have significant antitumour activity. The mechanism of action of these medicines is not known at present. PMID:18159975

  8. Inhibition of melanocortin 1 receptor slows melanoma growth, reduces tumor heterogeneity and increases survival.

    Science.gov (United States)

    Kansal, Rita G; McCravy, Matthew S; Basham, Jacob H; Earl, Joshua A; McMurray, Stacy L; Starner, Chelsey J; Whitt, Michael A; Albritton, Lorraine M

    2016-05-01

    Melanoma risk is increased in patients with mutations of melanocortin 1 receptor (MC1R) yet the basis for the increased risk remains unknown. Here we report in vivo evidence supporting a critical role for MC1R in regulating melanoma tumor growth and determining overall survival time. Inhibition of MC1R by its physiologically relevant competitive inhibitor, agouti signaling protein (ASIP), reduced melanin synthesis and morphological heterogeneity in murine B16-F10 melanoma cells. In the lungs of syngeneic C57BL/6 mice, mCherry-marked, ASIP-secreting lung tumors inhibited MC1R on neighboring tumors lacking ASIP in a dose dependent manner as evidenced by a proportional loss of pigment in tumors from mice injected with 1:1, 3:1 and 4:1 mixtures of parental B16-F10 to ASIP-expressing tumor cells. ASIP-expressing B16-F10 cells formed poorly pigmented tumors in vivo that correlated with a 20% longer median survival than those bearing parental B16-F10 tumors (p=0.0005). Mice injected with 1:1 mixtures also showed survival benefit (p=0.0054), whereas injection of a 4:1 mixture showed no significant difference in survival. The longer survival time of mice bearing ASIP-expressing tumors correlated with a significantly slower growth rate than parental B16-F10 tumors as judged by quantification of numbers of tumors and total tumor load (p=0.0325), as well as a more homogeneous size and morphology of ASIP-expressing lung tumors. We conclude that MC1R plays an important role in regulating melanoma growth and morphology. Persistent inhibition of MC1R provided a significant survival advantage resulting in part from slower tumor growth, establishing MC1R as a compelling new molecular target for metastatic melanoma. PMID:27028866

  9. Melanoma - neck (image)

    Science.gov (United States)

    This melanoma on the neck is variously colored with a very darkly pigmented area found centrally. It has irregular ... be larger than 0.5 cm. Prognosis in melanoma is best defined by its depth on resection.

  10. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  11. Treatment Option Overview (Melanoma)

    Science.gov (United States)

    ... of Skin Cancer Skin Cancer Screening Research Melanoma Treatment (PDQ®)–Patient Version General Information About Melanoma Key ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  12. General Information about Melanoma

    Science.gov (United States)

    ... Screening Research Melanoma Treatment (PDQ®)–Patient Version General Information About Melanoma Go to Health Professional Version Key ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  13. Melanoma inhibitory activity in Brazilian patients with cutaneous melanoma*

    OpenAIRE

    Odashiro, Macanori; Hans Filho, Gunter; Pereira, Patricia Rusa; Castro, Ana Rita Coimbra Motta; Stief, Alcione Cavalheiro; Pontes, Elenir Rose Jardim Cury; Odashiro, Alexandre Nakao

    2015-01-01

    BACKGROUND: Melanoma inhibitory activity is a protein secreted by melanoma cells and has been used as a tumor marker. Increased Melanoma inhibitory activity serum levels are related to metastatic disease or tumor recurrence. Currently there are no studies on Melanoma inhibitory activity and cutaneous melanoma involving Brazilian patients. OBJECTIVE: To evaluate the performance and feasibility of measuring Melanoma inhibitory activity levels in Brazilian patients with cutaneous melanoma. METHO...

  14. Novel alpha-MSH peptide analogs for melanoma targeting

    Science.gov (United States)

    Flook, Adam Michael

    Skin cancer is the one of the most diagnosed cancers in the United States with increasing incidence over the past two decades. There are three major forms of skin cancer but melanoma is the deadliest. It is estimated that 76,690 new diagnoses of melanoma and 9,480 deaths will occur in 2013. Melanoma accounts for approximately 1.6% of all cancer related deaths and is the 5 th leading diagnosed cancer in the United States. The mean survival rate of patients diagnosed with metastatic melanoma is six months, with five year survival rates of less than 5%. In this project, we describe the design and characterization of novel melanoma-targeting peptide analogs for use in diagnostic imaging of both primary and metastatic melanoma lesions. Novel alpha-MSH peptide conjugates were designed to target the melanocortin-1 receptor present and over-expressed on melanoma cells. These peptides were synthesized and their in-vitro melanocortin-1 receptor binding affinities were established in murine melanoma cells. Once binding affinities were determined, the peptides were radiolabeled with 99mTc utilizing a novel direct radiolabeling technique developed in our laboratory. The peptides were purified via reverse-phase high performance liquid chromatography and in-vivo melanoma targeting and pharmacokinetic properties were determined in B16/F1 melanoma-bearing female C57BL/6 mice. Biodistribution and SPECT/CT imaging studies were performed with the promising 99m Tc-labeled peptide conjugates. All alpha-MSH peptide conjugates tested showed low nanomolar binding affinity for the melanocortin-1 receptor. All peptides were readily radiolabeld with 99mTc with greater than 95% radiochemical purity. All 99mTc-labeled peptides displayed high specific in-vivo melanoma tumor uptake while maintaining low normal organ accumulation, and were excreted through the urinary system in a timely fashion. In addition, all tested 99mTc-labeld alpha-MSH peptides demonstrated clear visualization of in

  15. Label-free detection of circulating melanoma cells by in vivo photoacoustic flow cytometry

    Science.gov (United States)

    Wang, Xiaoling; Yang, Ping; Liu, Rongrong; Niu, Zhenyu; Suo, Yuanzhen; He, Hao; Gao, Wenyuan; Tang, Shuo; Wei, Xunbin

    2016-03-01

    Melanoma is a malignant tumor of melanocytes. Melanoma cells have high light absorption due to melanin highly contained in melanoma cells. This property is employed for the detection of circulating melanoma cell by in vivo photoacoustic flow cytometry (PAFC), which is based on photoacoustic effect. Compared to in vivo flow cytometry based on fluorescence, PAFC can employ high melanin content of melanoma cells as endogenous biomarkers to detect circulating melanoma cells in vivo. We have developed in vitro experiments to prove the ability of PAFC system of detecting photoacoustic signals from melanoma cells. For in vivo experiments, we have constructed a model of melanoma tumor bearing mice by inoculating highly metastatic murine melanoma cancer cells, B16F10 with subcutaneous injection. PA signals are detected in the blood vessels of mouse ears in vivo. The raw signal detected from target cells often contains some noise caused by electronic devices, such as background noise and thermal noise. We choose the Wavelet denoising method to effectively distinguish the target signal from background noise. Processing in time domain and frequency domain would be combined to analyze the signal after denoising. This algorithm contains time domain filter and frequency transformation. The frequency spectrum image of the signal contains distinctive features that can be used to analyze the property of target cells or particles. The processing methods have a great potential for analyzing signals accurately and rapidly. By counting circulating melanoma cells termly, we obtain the number variation of circulating melanoma cells as melanoma metastasized. Those results show that PAFC is a noninvasive and label-free method to detect melanoma metastases in blood or lymph circulation.

  16. Stress indices for ANSI standard B16.11 socket-welding fittings

    International Nuclear Information System (INIS)

    Stress indices for ANSI standard B16.11 socket-welding tees, 450 elbows, 900 elbows, and couplings are developed for intended use with the Class-1 piping system design rules of Section III--Division 1 of the ASME Boiler and Pressure Vessel Code. Indices are given for the evaluation of appropriate primary stresses, primary-plus-secondary stresses, and peak stresses due to internal pressure, bending-moment loads, and thermal gradients between the fitting and the attached pipe. The proposed indices are based on the dimensional and pressure-burst requirements of the B16.11 standard, the apparent shapes of B16.11 fittings as indicated from a random sampling taken off-the-shelf, the standard pressure-temperature ratings of the fittings, and on current stress indices now in the Code for similar butt-welding fittings. Specific recommendations are made for issuing the new stress indices in a Code case. (auth)

  17. Treatment of mouse melanoma cells with phorbol 12-myristate 13-acetate counteracts mannosylerythritol lipid-induced growth arrest and apoptosis

    OpenAIRE

    Zhao, Xiaoxian; Geltinger, Christian; Kishikawa, Shotaro; Ohshima, Kiyoshi; Murata, Takehide; Nomura, Nobuhiko; Nakahara, Tadaatsu; Yokoyama, Kazunari K.

    2000-01-01

    Mannosylerythritol lipid (MEL), an extracellularglycolipid from yeast, induces the differentiation ofHL-60 promyelocytic leukemia cells towardsgranulocytes. We show here that MEL is also a potentinhibitor of the proliferation of mouse melanoma B16cells. Flow-cytometric analysis of the cell cycle ofMEL-treated B16 cells revealed the accumulation ofcells in the sub-G0/G1 phase, which is a hallmark ofcells undergoing apoptosis. Treatment of B16 cellsfor 24 h with phorbol 12-myristate 13-acetate ...

  18. Malignant melanoma - cutaneous metastases

    OpenAIRE

    Padmavathy L; Rao L; Ethirajan N; Swamy B

    2008-01-01

    Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra.1 Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported.

  19. Genetics of familial melanoma

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin A W; Pritchard, Antonia L;

    2015-01-01

    Twenty years ago, the first familial melanoma susceptibility gene, CDKN2A, was identified. Two years later, another high-penetrance gene, CDK4, was found to be responsible for melanoma development in some families. Progress in identifying new familial melanoma genes was subsequently slow; however...

  20. Burden of Melanoma

    NARCIS (Netherlands)

    C. Holterhues (Cynthia)

    2011-01-01

    markdownabstract__Abstract__ Melanoma is a type of skin cancer that arises from melanocytes. More than 95% of all melanomas occur in the skin, but rarely in the pigmented cells of the eye, meninges or mucosa. This thesis will only regard the invasive cutaneous malignant melanomas.

  1. Vaccine Therapy in Treating Patients With Stage IIC-IV Melanoma

    Science.gov (United States)

    2014-05-20

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Mucosal Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage IIC Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIA Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIB Melanoma; Stage IIIC Intraocular Melanoma; Stage IIIC Melanoma; Stage IV Intraocular Melanoma; Stage IV Melanoma

  2. Radioiodide uptake in melanoma cells after transfer of human NaI symporter gene

    Institute of Scientific and Technical Information of China (English)

    CHEN Li-Bo; ZHU Rui-Sen; LU Han-Kui; YU Yong-Li; LUO Quan-Yong; HUANG Fang; FEI Jian; GUO Li-He

    2004-01-01

    To obtain human sodium/iodide symporter gene cDNA for studying its potential ability as a radioiodide treatment for melanoma, the hNIS gene cDNA was amplified with total RNA from human thyroid tissue by RT-PCR.The hNIS cDNA was inserted into cloning vector pUCm-T and subcloned into eukaryotic expression vector pc-DNA3.The pc-DNA3-hNIS and pc-DNA3 were transduced into melanoma cells (B 16) by electroporation, and two cell lines termed B 16-A and B16-B respectively were established. The uptake and efflux of iodide was examined in vitro. The three cell lines (B16-A, B16-B, B16) were injected subcutaneously into the right flank of C57 mice. Biodistribution study and tumor imaging were performed when the tumor reached approximately 10mm in diameter. The cloned hNIS cDNA sequence was identical with the published sequence. Two novel cell lines named 16-A containing pc-DNA3-hNIS and B16-B containing pc-DNA3 only were established. The resultant cell line B16-A accumulated 17and 19 times more radioiodide in vitro than B 16 and B 16-B respectively. The iodide uptake reached the half-maximal level within 10 min, and reached a plateau at 30 min. The efflux of iodide was also rapid (T1/2cff=10min). The imaging shows in vivo uptake in expected sites including the salivary glands, thyroid, stomach, and hNIS-transduced tumor,whereas the nontransduced tumor was not visualized. The %ID/g of B 16-A tumors at 1, 2, 4, 12, and 24h after injection of 125I were 12.22±0.71, 10.91±0.72, 8.73±0.99, 1.24±0.29, and 0.19±0.03, respectively, which were signifi cantly higher percentages than those for controlling tumors, p<0.01. However, biologic T1/2 was about 6 h. Our preliminary data indicate that the transduction of the hNIS gene per se is sufficient to induce iodide transport in melanoma cells both in vitro and in vivo, but T1/2eff is short.

  3. 131/123 iodine labeled benzamides for the detection of melanomas and metastases. Synthesis, labeling, animal experiences and preliminary clinical studies

    International Nuclear Information System (INIS)

    Radioiodine labeled benzamides are being studied as radiopharmaceuticals for the detection of melanomas and metastases. With this purpose the synthesis and labeling of N-(2-diethylaminoethyl)-3-[131I]-4-methoxybenzamide (IMBA) has been carried out. Tissue distribution of the labeled compound has been studied in C 57 mice, showing a fast renal excretion. The labeled benzamide was also injected in mice with previously induced subcutaneous melanomas and lung metastases using B 16-F0 murine melanoma cells. The tumors show a good uptake of the labeled benzamide. The melanoma/other tissues uptake ratio is suitable for scintigraphic detection. Clinical studies in patients are under way. (author)

  4. Estudio tribológico comparativo de los Babbits Fórmula V y B-16 // Babbits comparative Study About Fórmulas V and B-16

    OpenAIRE

    M. Díaz Díaz; C. Díaz Novo; O. Calderín Medina

    1999-01-01

    En el trabajo se realiza un estudio comparativo del coeficiente de fricción de los Babbits, fórmula V y B-16, así como lainfluencia que ejerce sobre estos la presión de trabajo y el ángulo de contacto entre el cojinete y el árbol, determinándose lasexpresiones empíricas que rigen esta relación para ambos materiales antifricción.Palabras claves: Babbi t s, presión, angulo de contacto, coj inetes de desl izamiento._________________________________________________________________________________...

  5. Evaluation of two (125)I-radiolabeled acridine derivatives for Auger-electron radionuclide therapy of melanoma.

    Science.gov (United States)

    Gardette, Maryline; Viallard, Claire; Paillas, Salomé; Guerquin-Kern, Jean-Luc; Papon, Janine; Moins, Nicole; Labarre, Pierre; Desbois, Nicolas; Wong-Wah-Chung, Pascal; Palle, Sabine; Wu, Ting-Di; Pouget, Jean-Pierre; Miot-Noirault, Elisabeth; Chezal, Jean-Michel; Degoul, Francoise

    2014-08-01

    We previously selected two melanin-targeting radioligands [(125)I]ICF01035 and [(125)I]ICF01040 for melanoma-targeted (125)I radionuclide therapy according to their pharmacological profile in mice bearing B16F0 tumors. Here we demonstrate in vitro that these compounds present different radiotoxicities in relation to melanin and acidic vesicle contents in B16F0, B16F0 PTU and A375 cell lines. ICF01035 is effectively observed in nuclei of achromic (A375) melanoma or in melanosomes of melanized melanoma (B16F0), while ICF01040 stays in cytoplasmic vesicles in both cells. [(125)I]ICF01035 induced a similar survival fraction (A50) in all cell lines and led to a significant decrease in S-phase cells in amelanotic cell lines. [(125)I]ICF01040 induced a higher A50 in B16 cell lines compared to [(125)I]ICF01035 ones. [(125)I]ICF01040 induced a G2/M blockade in both A375 and B16F0 PTU, associated with its presence in cytoplasmic acidic vesicles. These results suggest that the radiotoxicity of [(125)I]ICF01035 and [(125)I]ICF01040 are not exclusively reliant on DNA alterations compatible with γ rays but likely result from local dose deposition (Auger electrons) leading to toxic compound leaks from acidic vesicles. In vivo, [(125)I]ICF01035 significantly reduced the number of B16F0 lung colonies, enabling a significant increase in survival of the treated mice. Targeting melanosomes or acidic vesicles is thus an option for future melanoma therapy. PMID:24691673

  6. Study of structural transformations in Fe83W1B16 alloy resulting from natural aging

    International Nuclear Information System (INIS)

    Structural transformations taking place in amorphous Fe83W1B16 alloy as a result of its natural aging are investigated by Moessbauer spectroscopy and thermomagnetic analysis methods. Spatial inhomogeneity of changes in the atom closest vicinity and its effect on the alloy magnetization temperature dependence progress are ascertained. 9 refs.; 3 figs

  7. Liver Transplant

    Science.gov (United States)

    ... Home > Your Liver > Liver Disease Information > Liver Transplant Liver Transplant Explore this section to learn more about liver ... harmful substances from your blood. What is a liver transplant? A liver transplant is the process of replacing ...

  8. CDC Vital Signs: Preventing Melanoma

    Science.gov (United States)

    ... Press Kit Read the MMWR Science Clips Preventing Melanoma Communities Play a Vital Role Language: English Español ( ... and use of indoor tanning by minors. Problem Melanoma is increasing. Melanoma skin cancer is common and ...

  9. Effect of Adipocyte Secretome in Melanoma Progression and Vasculogenic Mimicry.

    Science.gov (United States)

    Coelho, Pedro; Almeida, Joana; Prudêncio, Cristina; Fernandes, Rúben; Soares, Raquel

    2016-07-01

    Obesity, favored by the modern lifestyle, acquired epidemic proportions nowadays. Obesity has been associated with various major causes of death and morbidity including malignant neoplasms. This increased prevalence has been accompanied by a worldwide increase in cutaneous melanoma incidence rates during the last decades. Obesity involvement in melanoma aetiology has been recognized, but the implicated mechanisms remain unclear. In the present study, we address this relationship and investigate the influence of adipocytes secretome on B16-F10 and MeWo melanoma cell lines. Using the 3T3-L1 adipocyte cell line, as well as ex vivo subcutaneous (SAT) and visceral (VAT) adipose tissue conditioned medium, we were able to show that adipocyte-released factors play a dual role in increasing melanoma cell overall survival, both by enhancing proliferation and decreasing apoptosis. B16-F10 cell migration and cell-cell and cell-matrix adhesion capacity were predominantly enhanced in the presence of SAT and VAT released factors. Melanocytes morphology and melanin content were also altered by exposure to adipocyte conditioned medium disclosing a more dedifferentiated phenotype of melanocytes. In addition, exposure to adipocyte-secreted molecules induced melanocytes to rearrange, on 3D cultures, into vessel-like structures, and generate characteristic vasculogenic mimicry patterns. These findings are corroborated by the released factors profile of 3T3-L1, SAT, and VAT assessed by microarrays, and led us to highlight the mechanisms by which adipose secretome from sub-cutaneous or visceral depots promote melanoma progression. J. Cell. Biochem. 117: 1697-1706, 2016. © 2015 Wiley Periodicals, Inc. PMID:26666522

  10. Effects of Genistein on Cell Cycle and Apoptosis of Two Murine Melanoma Cell Lines

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The effects of genistein on several tumor cell lines were investigated to study the effects of genistein on cell growth, cell cycle, and apoptosis of two murine melanoma cell lines, B16 and K1735M2. These two closely related murine melanoma cell lines, however, have different responses to the genistein treatment. Genistein inhibits the growth of both the B16 and K1735M2 cell lines and arrests the growth at the G2/M phase. After treatment with 60 μmol/L genistein for 72 h, apoptosis and caspase activities were detected in B16 cells, while such effects were not found in K1735M2. Further tests showed that after genistein treatment the protein content and mRNA levels of p53 increased in B16, but remained the same in K1735M2. The protein content and mRNA levels of p21WAF1/CIP1 increased in both cell lines after treatment.The results show that genistein might induce apoptosis in B16 cells by damaging the DNA, inhibiting topoisomerase Ⅱ, increasing p53 expression, releasing cytochrome c from the mitochondria, and activating the caspases which will lead to apoptosis.

  11. Effect of low frequency magnetic fields on melanoma: tumor inhibition and immune modulation

    International Nuclear Information System (INIS)

    We previously found that the low frequency magnetic fields (LF-MF) inhibited gastric and lung cancer cell growth. We suppose that exposure to LF-MF may modulate immune function so as to inhibit tumor. We here investigated whether LF-MF can inhibit the proliferation and metastasis of melanoma and influence immune function. The effect of MF on the proliferation, cell cycle and ultrastracture of B16-F10 in vitro was detected by cell counting Kit-8 assay, flow cytometry, and transmission electron microscopy. Lung metastasis mice were prepared by injection of 2 × 105 B16-F10 melanoma cells into the tail vein in C57BL/6 mice. The mice were then exposed to an LF-MF (0.4 T, 7.5 Hz) for 43 days. Survival rate, tumor markers and the innate and adaptive immune parameters were measured. The growth of B16-F10 cells was inhibited after exposure to the LF-MF. The inhibition was related to induction of cell cycle arrest and decomposition of chromatins. Moreover, the LF-MF prolonged the mouse survival rate and inhibited the proliferation of B16-F10 in melanoma metastasis mice model. Furthermore, the LF-MF modulated the immune response via regulation of immune cells and cytokine production. In addition, the number of Treg cells was decreased in mice with the LF-MF exposure, while the numbers of T cells as well as dendritic cells were significantly increased. LF-MF inhibited the growth and metastasis of melanoma cancer cells and improved immune function of tumor-bearing mice. This suggests that the inhibition may be attributed to modulation of LF-MF on immune function and LF-MF may be a potential therapy for treatment of melanoma

  12. Decoding Melanoma Metastasis

    International Nuclear Information System (INIS)

    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis

  13. Are all melanomas dangerous?

    DEFF Research Database (Denmark)

    Nørgaard, Carsten; Glud, Martin; Gniadecki, Robert

    2011-01-01

    The increased incidence of cutaneous malignant melanoma, together with only minor changes in mortality, has brought into question the existence of a melanoma epidemic. The discrepancy between incidence and mortality suggests that most newly diagnosed melanomas have indolent behaviour. This review...... summarizes the most recent epidemiological findings regarding the incidence of cutaneous malignant melanoma, mortality, Breslow thickness and clinical stage. Studies published between 2005 and 2010 with more than 2,000 test subjects were included in this review. These studies all report an increase in...... incidence of melanoma during the last few decades, with by far the highest increase in tumours at a very early stage (T1 or IA). Little or no change was seen in mortality. However, increases in both mortality and incidence of thick melanomas were found in the oldest subgroups, especially in men. These...

  14. Decoding Melanoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Damsky, William E. Jr. [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States); Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont (United States); Rosenbaum, Lara E.; Bosenberg, Marcus, E-mail: Marcus.Bosenberg@yale.edu [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States)

    2010-12-30

    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  15. Carbon ion induced DNA double-strand breaks in melanophore B16

    International Nuclear Information System (INIS)

    DNA double-strand breaks (DSBs) in melanophore B16 induced by plateau and extended Bragg peak of 75 MeV/u 12C6+ ions were studied by using a technique of inverse pulsed-field gel electrophoresis (PIGE). DNA fragment lengths were distributed in two ranges: the larger in 1.4 Mbp-3.2 Mbp and the smaller in less than 1.2 Mbp. It indicates that distribution of DNA fragments induced by heavy ion irradiation is not stochastic and there probably are sensitive sites to heavy ions in DNA molecules of B16. Percentage of DNA released from plug (PR) increased and trended towards a quasi-plateau ∝85% as dose increased. Content of the larger fragments decreased and flattened with increasing dose while content of the smaller ones increased and trended towards saturation. (orig.)

  16. Malignant melanoma - cutaneous metastases

    Directory of Open Access Journals (Sweden)

    Padmavathy L

    2008-01-01

    Full Text Available Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra. Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported.

  17. Malignant melanoma - cutaneous metastases.

    Science.gov (United States)

    L, Padmavathy; L, Lakshmana Rao; N, Ethirajan; B, Krishna Swamy

    2008-01-01

    Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra.1 Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported. PMID:19882041

  18. Comparative study of angio genesis radiopharmaceuticals for melanoma detection

    International Nuclear Information System (INIS)

    Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 μL of a μg/μL solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for 99mTc-MAG3-PEG8-c(RGDyK) (7.85±±2.34 %ID/g) at 120 min post injection. The performance of 99mTc-MAG3-PEG8-c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

  19. Melanoma Therapy via Peptide-Targeted a-Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Yubin; Hylarides, Mark; Fisher, Darrell R.; Shelton, Tiffani; Moore, Herbert A.; Wester, Dennis W.; Fritzberg, Alan R.; Winkelmann, Christopher T.; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-08-01

    Malignant melanoma is the most lethal form of skin cancer. Current chemotherapy and external beam radiation therapy regimens are ineffective agents against melanoma, as shown by a 10-year survival rate for patients with disseminated disease of approximately 5% (reference?). In this study, the unique combination of a melanoma targeting peptide and an in vivo generated a-particle emitting radioisotope was investigated for its melanoma therapy potential. Alpha-radiation is densely ionizing and energy is locally absorbed, resulting in high concentrations of destructive free radicals and irreparable DNA double strand breaks. This high linear-energy-transfer overcomes radiation resistant tumor cells and oxygen-enhancement effects. The melanoma targeting peptide DOTA-Re(Arg11)CCMSH was radiolabeled with 212Pb, the parent of 212Bi, which decays via alpha and beta decay. Biodistribution and therapy studies were performed in the B16/F1 melanoma bearing C57 mouse flank tumor model. 212Pb[DOTA]-R e(Arg11)CCMSH exhibited rapid tumor uptake and extended retention coupled with rapid whole body disappearance. Radiation dose delivered to the tumor was estimated to be 61 cGy/uCi 212Pb administered. Treatment of melanoma-bearing mice with 50, 100 and 200 uCi of 212Pb[DOTA]-Re(Arg11)CCMSH extended mean survival of mice to 22, 28, and 49.8 days, respectively, compared to the 14.6 day mean survival of the placebo control group. Forty-five percent of the mice receiving 200 uCi survived the study disease-free.

  20. Docosahexaenoic acid inhibits melanin synthesis in murine melanoma cells in vitro through increasing tyrosinase degradation

    OpenAIRE

    Balcos, Marie Carmel; Kim, Su Yeon; Jeong, Hyo-Soon; Yun, Hye-Young; Baek, Kwang Jin; Kwon, Nyoun Soo; Park, Kyoung-Chan; Kim, Dong-Seok

    2014-01-01

    Aim: To investigate the effects of docosahexaenoic acid (DHA) on melanin synthesis and related regulatory mechanisms. Methods: B16F10 mouse melanoma cells were exposed to DHA for 3 d, and melanin content and tyrosinase activity were measured. Western blot analysis was used to analyze the protein levels in DHA-mediated signal transduction pathways. Results: DHA (1–25 μmol/L) did not affect the viability of B16F10 cells, but decreased α-MSH-induced melanin synthesis in a concentration-dependent...

  1. Properties of kojic acid and curcumin: Assay on cell B16-F1

    Science.gov (United States)

    Sugiharto, Ariff, Arbakariya; Ahmad, Syahida; Hamid, Muhajir

    2016-03-01

    Ultra violet (UV) exposure and oxidative stress are casually linked to skin disorders. They can increase melanin synthesis, proliferation of melanocytes, and hyperpigmentation. It is possible that antioxidants or inhibitors may have a beneficial effect on skin health to reduce hyperpigmentation. In the last few years, a huge number of natural herbal extracts have been tested to reduce hyperpigmentation. The objective of this study was to determine and to compare of kojic acid and curcumin properties to viability cell B16-F1. In this study, our data showed that the viability of cell B16-F1 was 63.91% for kojic acid and 64.12% for curcumin at concentration 100 µg/ml. Further investigation assay of antioxidant activities, indicated that IC50 for kojic acid is 63.8 µg/ml and curcumin is 16.05 µg/ml. Based on the data, kojic acid and curcumin have potential antioxidant properties to reduce hyperpigmentation with low toxicity effect in cell B16-F1.

  2. Changes in intestinal microflora of Caenorhabditis elegans following Bacillus nematocida B16 infection.

    Science.gov (United States)

    Niu, Qiuhong; Zhang, Lin; Zhang, Keqin; Huang, Xiaowei; Hui, Fengli; Kan, Yunchao; Yao, Lunguang

    2016-01-01

    The effect of pathogenic bacteria on a host and its symbiotic microbiota is vital and widespread in the biotic world. The soil-dwelling opportunistic bacterium Bacillus nematocida B16 uses a "Trojan horse" mechanism to kill Caenorhabditis elegans. The alterations in the intestinal microflora that occur after B16 infection remain unknown. Here, we analyzed the intestinal bacteria presented in normal and infected worms. The gut microbial community experienced a complex change after B16 inoculation, as determined through marked differences in species diversity, structure, distribution and composition between uninfected and infected worms. Regardless of the worm's origin (i.e., from soil or rotten fruits), the diversity of the intestinal microbiome decreased after infection. Firmicutes increased sharply, whereas Proteobacteria, Actinobacteria, Cyanobacteria and Acidobacteria decreased to different degrees. Fusobacteria was only present 12 h post-infection. After 24 h of infection, 1228 and 1109 bacterial species were identified in the uninfected and infected groups, respectively. The shared species reached 21.97%. The infected group had a greater number of Bacillus species but a smaller number of Pediococcus, Halomonas, Escherichia and Shewanella species (P microbiota using C. elegans as the model species. PMID:26830015

  3. Comparative study of angio genesis radiopharmaceuticals for melanoma detection; Estudo comparativo de radiofarmacos para angiogenese na deteccao de melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Erica Aparecida de

    2011-07-01

    Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 {mu}L of a {mu}g/{mu}L solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for {sup 99m}Tc-MAG3-PEG{sub 8}-c(RGDyK) (7.85{+-}{+-}2.34 %ID/g) at 120 min post injection. The performance of {sup 99m}Tc-MAG{sub 3}-PEG{sub 8}-c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

  4. Expression and functions of galectin-7 in human and murine melanomas.

    Directory of Open Access Journals (Sweden)

    Katherine Biron-Pain

    Full Text Available The identification of galectin-7 as a p53-induced gene and its ability to induce apoptosis in many cell types support the hypothesis that galectin-7 has strong antitumor activity. This has been well documented in colon cancer. However, in some cases, such as breast cancer and lymphoma, its high expression level correlates with aggressive subtypes of cancer, suggesting that galectin-7 may have a dual role in cancer progression. In fact, in breast cancer, overexpression of galectin-7 alone is sufficient to promote metastasis to the bone and lung. In the present work, we investigated the expression and function of galectin-7 in melanoma. An analysis of datasets obtained from whole-genome profiling of human melanoma tissues revealed that galectin-7 mRNA was detected in more than 90% of biopsies of patients with nevi while its expression was more rarely found in biopsies collected from patients with malignant melanoma. This frequency, however, was likely due to the presence of normal epidermis tissues in biopsies, as shown our studies at the protein level by immunohistochemical analysis. Using the experimental melanoma B16F1 cell line, we found that melanoma cells can express galectin-7 at the primary tumor site and in lung metastasis. Moreover, we found that overexpression of galectin-7 increased the resistance of melanoma cells to apoptosis while inducing de novo egr-1 expression. Overexpression of galectin-7, however, was insufficient to modulate the growth of tumors induced by the subcutaneous injection of B16F1 cells. It also failed to modulate the dissemination of B16F1 cells to the lung.

  5. Macrophages elicited with heat-killed bacillus Calomette-Guerin protect C57BL/6J mice against a syngeneic melanoma

    OpenAIRE

    1980-01-01

    We have demonstrated that a murine cytotoxic peritoneal cell can be elicited by intraperitoneal immunization with heat-killed Mycobacterium bovis, strain Bacillus Calmette-Guerin (BCG). When these cells are injected together with cells of clone B(5)59 of B16 melanoma in a Winn- type transfer assay into syngeneic C57BL/6J mice, the tumorigenic potential of the melanoma is completely abrogated. Similarly, mice immunized intraperitoneally with dead BCG are protected against intraperitoneal chall...

  6. Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice

    Directory of Open Access Journals (Sweden)

    Takafumi Imai

    2015-02-01

    Full Text Available Previous studies using B16BL6-derived exosomes labelled with gLuc–lactadherin (gLuc-LA, a fusion protein of Gaussia luciferase (a reporter protein and lactadherin (an exosome-tropic protein, showed that the exosomes quickly disappeared from the systemic circulation after intravenous injection in mice. In the present study, the mechanism of rapid clearance of intravenously injected B16BL6 exosomes was investigated. gLuc-LA-labelled exosomes were obtained from supernatant of B16BL6 cells after transfection with a plasmid DNA encoding gLuc-LA. Labelling was stable when the exosomes were incubated in serum. By using B16BL6 exosomes labelled with PKH26, a lipophilic fluorescent dye, it was demonstrated that PKH26-labelled B16BL6 exosomes were taken up by macrophages in the liver and spleen but not in the lung, while PKH26-labelled exosomes were taken up by the endothelial cells in the lung. Subsequently, gLuc-LA-labelled B16BL6 exosomes were injected into macrophage-depleted mice prepared by injection with clodronate-containing liposomes. The clearance of the intravenously injected B16BL6 exosomes from the blood circulation was much slower in macrophage-depleted mice than that in untreated mice. These results indicate that macrophages play important roles in the clearance of intravenously injected B16BL6 exosomes from the systemic circulation.

  7. Synthesis and evaluation of novel radioiodinated nicotinamides for malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Liu Xiang; Pham, Tien Q.; Berghofer, Paula; Chapman, Janette; Greguric, Ivan; Mitchell, Peter; Mattner, Filomena; Loc' h, Christian [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Sydney, NSW 2234 (Australia); Katsifis, Andrew [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Sydney, NSW 2234 (Australia)], E-mail: akx@ansto.gov.au

    2008-10-15

    Introduction: A series of iodonicotinamides based on the melanin-binding iodobenzamide compound N-2-diethylaminoethyl-4-iodobenzamide was prepared and evaluated for the potential imaging and staging of disseminated metastatic melanoma. Methods: [{sup 123}I]Iodonicotinamides were prepared by iododestannylation reactions using no-carrier-added iodine-123 and evaluated in vivo by biodistribution and competition studies and by single photon emission computed tomography (SPECT) imaging in black and albino nude mice bearing B16F0 murine melanotic and A375 human amelanotic melanoma tumours, respectively. Results: The iodonicotinamides displayed low-affinity binding for {sigma}{sub 1}-{sigma}{sub 2} receptors (K{sub i}>300 nM). In biodistribution studies in mice, N-(2-(diethylamino)ethyl)-5-[{sup 123}I]iodonicotinamide ([{sup 123}I]1) exhibited the fastest and highest uptake of the nicotinamide series in the B16F0 tumour at 1 h ({approx}8% ID/g), decreasing slowly over time. No uptake was observed in the A375 tumour. Clearance from the animals by urinary excretion was more rapid for N-alkyl-nicotinamides than for piperazinyl derivatives. At 1 h postinjection, the urinary excretion was 66% ID for [{sup 123}I]1, while the gastrointestinal tract amounted to 17% ID. Haloperidol was unable to reduce the uptake of [{sup 123}I]1 in pigmented mice, indicating that this uptake was likely due to an interaction with melanin. SPECT imaging of [{sup 123}I]1 in black mice bearing the B16F0 melanoma indicated that the radioactivity was predominately located in the tumour and eyes. No specific localisation was observed in nude mice bearing A375 amelanotic tumours. Conclusion: These findings suggest that [{sup 123}I]1, which displays high tumour uptake with rapid clearance from the body, could be a promising imaging agent for the detection of melanotic tumours.

  8. Blockade of PD-L1 Enhances the Therapeutic Efficacy of Combination Immunotherapy Against Melanoma1

    OpenAIRE

    Pilon-Thomas, Shari; Mackay, Amy; Vohra, Nasreen; Mulé, James J

    2010-01-01

    Inhibition of anti-tumor T cell responses can be mediated by the productive interaction between the programmed death-1 (PD-1) receptor on T cells and its ligand PD-L1. PD-L1 is highly expressed on both murine bone marrow-derived dendritic cells (DC) and B16 melanoma. In this study, in vitro blockade of PD-L1 interaction on DC led to enhanced IFN-gamma production and cytotoxicity by antigen-specific T cells. In vivo, the systemic administration of anti-PD-L1 antibody plus melanoma peptide-puls...

  9. Are all melanomas dangerous?

    DEFF Research Database (Denmark)

    Nørgaard, Carsten; Glud, Martin; Gniadecki, Robert

    2011-01-01

    incidence of melanoma during the last few decades, with by far the highest increase in tumours at a very early stage (T1 or IA). Little or no change was seen in mortality. However, increases in both mortality and incidence of thick melanomas were found in the oldest subgroups, especially in men. These...

  10. Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients

    OpenAIRE

    Ramya Chockalingam; Christopher Downing; Tyring, Stephen K.

    2015-01-01

    Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC) are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent years, human papillomaviruses (HPV) of the beta genus have been implicated in the pathogenesis of post-transplant SCCs. The underlying mechanism of carcinogenesis has been attributed to the...

  11. Interleukin-6 and melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Schmidt, Henrik

    2012-01-01

    Interleukin-6 (IL-6) is a pleiotropic immunomodulatory cytokine produced by various types of cells, including melanoma cells. IL-6 plays a major role in the pathogenesis and development of malignancies. It promotes tumour growth by inhibition of apoptosis and induces tumour angiogenesis. IL-6 is...... deregulated in many types of cancers, and increased serum concentration of IL-6 has been correlated with a worse prognosis in patients with different cancers, including melanoma. Several serum cytokines including IL-6 play an important role in the development and progression of melanoma; however, the specific...... biological functions of IL-6 in progression of melanoma are unknown. In this review, we present studies on cell cultures and mouse models and summarize published clinical studies on IL-6 and melanoma....

  12. Single-walled carbon nanotube-conjugated chemotherapy exhibits increased therapeutic index in melanoma

    International Nuclear Information System (INIS)

    The incidence of malignant melanoma is increasing at an alarming rate globally. Poor prognosis and extraordinarily low survival rates of malignant melanoma necessitates the development of new chemotherapeutic strategies. An emerging approach is to harness nanotechnology to optimize the existing chemotherapies. In the present study we have demonstrated that the delivery of doxorubicin using a nanotechnology-based platform significantly reduces the systemic toxicity of the drug, keeping unchanged its therapeutic efficacy in a mouse melanoma tumor model. Specifically we modified single-walled carbon nanotubes (CNTs) to conjugate a doxorubicin prodrug via a carbamate linker that cleaves enzymatically to cause temporal release of the active drug. The CNT-doxorubicin conjugate (CNT-Dox) induced time-dependent cell death in B16-F10 melanoma cells in vitro. The nanoparticle was rapidly internalized into the lysosome of melanoma cells and was retained in the subcellular compartment for over 24 h. In an in vivo melanoma model, treatment with the nanotube-doxorubicin conjugate abrogated tumor growth without the systemic side-effects associated with free doxorubicin. Our studies demonstrate that a simple and versatile CNT-based nanovector can be harnessed for the delivery of chemotherapy to melanoma, with increased therapeutic index.

  13. In vivo, label-free, and noninvasive detection of melanoma metastasis by photoacoustic flow cytometry

    Science.gov (United States)

    Liu, Rongrong; Wang, Cheng; Hu, Cheng; Wang, Xueding; Wei, Xunbin

    2014-02-01

    Melanoma, a malignant tumor of melanocytes, is the most serious type of skin cancer in the world. It accounts for about 80% of deaths of all skin cancer. For cancer detection, circulating tumor cells (CTCs) serve as a marker for metastasis development, cancer recurrence, and therapeutic efficacy. Melanoma tumor cells have high content of melanin, which has high light absorption and can serve as endogenous biomarker for CTC detection without labeling. Here, we have developed an in vivo photoacoustic flow cytometry (PAFC) to monitor the metastatic process of melanoma cancer by counting CTCs of melanoma tumor bearing mice in vivo. To test in vivo PAFC's capability of detecting melanoma cancer, we have constructed a melanoma tumor model by subcutaneous inoculation of highly metastatic murine melanoma cancer cells, B16F10. In order to effectively distinguish the targeting PA signals from background noise, we have used the algorithm of Wavelet denoising method to reduce the background noise. The in vivo flow cytometry (IVFC) has shown a great potential for detecting circulating tumor cells quantitatively in the blood stream. Compared with fluorescence-based in vivo flow cytometry (IVFC), PAFC technique can be used for in vivo, label-free, and noninvasive detection of circulating tumor cells (CTCs).

  14. Single-walled carbon nanotube-conjugated chemotherapy exhibits increased therapeutic index in melanoma

    Science.gov (United States)

    Chaudhuri, Padmaparna; Soni, Shivani; Sengupta, Shiladitya

    2010-01-01

    The incidence of malignant melanoma is increasing at an alarming rate globally. Poor prognosis and extraordinarily low survival rates of malignant melanoma necessitates the development of new chemotherapeutic strategies. An emerging approach is to harness nanotechnology to optimize the existing chemotherapies. In the present study we have demonstrated that the delivery of doxorubicin using a nanotechnology-based platform significantly reduces the systemic toxicity of the drug, keeping unchanged its therapeutic efficacy in a mouse melanoma tumor model. Specifically we modified single-walled carbon nanotubes (CNTs) to conjugate a doxorubicin prodrug via a carbamate linker that cleaves enzymatically to cause temporal release of the active drug. The CNT-doxorubicin conjugate (CNT-Dox) induced time-dependent cell death in B16-F10 melanoma cells in vitro. The nanoparticle was rapidly internalized into the lysosome of melanoma cells and was retained in the subcellular compartment for over 24 h. In an in vivo melanoma model, treatment with the nanotube-doxorubicin conjugate abrogated tumor growth without the systemic side-effects associated with free doxorubicin. Our studies demonstrate that a simple and versatile CNT-based nanovector can be harnessed for the delivery of chemotherapy to melanoma, with increased therapeutic index.

  15. Single-walled carbon nanotube-conjugated chemotherapy exhibits increased therapeutic index in melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhuri, Padmaparna; Soni, Shivani; Sengupta, Shiladitya, E-mail: shiladit@mit.edu [BWH-HST Center for Biomedical Engineering, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, Harvard-MIT Division of Health Science and Technology, Cambridge, MA 02139 (United States)

    2010-01-15

    The incidence of malignant melanoma is increasing at an alarming rate globally. Poor prognosis and extraordinarily low survival rates of malignant melanoma necessitates the development of new chemotherapeutic strategies. An emerging approach is to harness nanotechnology to optimize the existing chemotherapies. In the present study we have demonstrated that the delivery of doxorubicin using a nanotechnology-based platform significantly reduces the systemic toxicity of the drug, keeping unchanged its therapeutic efficacy in a mouse melanoma tumor model. Specifically we modified single-walled carbon nanotubes (CNTs) to conjugate a doxorubicin prodrug via a carbamate linker that cleaves enzymatically to cause temporal release of the active drug. The CNT-doxorubicin conjugate (CNT-Dox) induced time-dependent cell death in B16-F10 melanoma cells in vitro. The nanoparticle was rapidly internalized into the lysosome of melanoma cells and was retained in the subcellular compartment for over 24 h. In an in vivo melanoma model, treatment with the nanotube-doxorubicin conjugate abrogated tumor growth without the systemic side-effects associated with free doxorubicin. Our studies demonstrate that a simple and versatile CNT-based nanovector can be harnessed for the delivery of chemotherapy to melanoma, with increased therapeutic index.

  16. Experimental stress analysis for four 24-in. ANSI standard B16.9 tees

    International Nuclear Information System (INIS)

    The experimental stress analysis and low cycle fatigue tests of four tees tested by Combustion Engineering, Inc. (E-E) under subcontract to Union Carbide Nuclear Division are described. These tests are part of the ORNL Design Criteria for Piping and Nozzles Program which is being conducted for the development of design criteria for nuclear power plant service piping components. The test assemblies were fabricated at C-E from commercially obtained ANSI B16.9 tees and matching diameter steel pipes welded to the tees, with suitable and closures and fixtures for applying the loads

  17. Lung transplant

    Science.gov (United States)

    ... lung transplants are done at the same time (heart-lung transplant) if the heart is also diseased. ... people develop cancers or have problems with the heart. For most ... transplant. They have better exercise endurance and are able ...

  18. Liver transplant

    Science.gov (United States)

    ... transplant - series References Keefe EB. Hepatic failure and liver transplantation. In: Goldman L, Schafer AI, eds. Goldman's Cecil ... Elsevier; 2011:chap 157. Martin P, Rosen HR. Liver transplantation. In: Feldman M, Friedman LS, Brandt LJ, eds. ...

  19. Transplant services

    Science.gov (United States)

    ... may be done with a kidney- pancreas transplant . Liver transplant may be the only option for someone with liver disease that has led to liver failure. Lung transplant may replace one or both lungs. It may ...

  20. Transfer of the human sodium/iodide symporter gene enhances iodide uptake in melanoma cells

    International Nuclear Information System (INIS)

    Aim: Radioiodide therapy using 131I is effective for patients who have benign thyroid diseases or differentiated thyroid carcinoma. The transport of iodide across the cell membrane is mediated by the human sodium/iodide symporter (hNIS). To investigate the feasibility of 131I therapy for melanoma, we established melanoma cells stably expressing hNIS gene that can be modulated and studied in vivo and in vitro. Material and Methods: We transfected hNIS gene into a mouse melanoma cell line (B16) by electroporation. Iodide accumulation was assessed under various extracellular concentrations of sodium and iodide, and iodide efflux was also evaluated. Biodistribution and tumor imaging were studied using tumor-bearing mice. Results: We established a novel cell line B16-3 stably expressing the hNIS gene from B16. 125I uptake by B16-3 cells is between 6-17-fold that of B16 cells and 8-33-fold that of cell lines transduced with the eukaryotic expression vector pcDNA3 only. Iodide uptake was completely inhibited by 1mmol/L perchlorate and was dependent on external sodium and iodide concentrations. The velocity of iodide efflux from B16-3 cells was almost equal to that of FRTL-5 thyroid cells (T1/2 = 4min). In the biodistribution study using B16-3-xenografted mice, high tumor uptake of 131I was shown at 1 hour after injection, and tumor-to-normal tissue ratios were also high, except in the thyroid and stomach. However, the residual iodide in tumor lessened with time, reaching less than 3% at 24 h after injection. Conclusion: The transduction of he hNIS gene per se is sufficient to induce iodide transport in melanoma cells in vivo and in vitro. With regard to therapeutic application, however, further investigation is necessary to determine a method of maintaining radioiodide in the cells long enough to produce greater therapeutic effects

  1. Analysis of a novel highly metastatic melanoma cell line identifies osteopontin as a new lymphangiogenic factor

    OpenAIRE

    Liersch, Ruediger; Shin, Jay W.; Bayer, Michael; Schwöppe, Christian; SCHLIEMANN, CHRISTOPH; Berdel, Wolfgang E.; Mesters, Rolf; Detmar, Michael

    2012-01-01

    Tumor cell invasion and metastasis are hallmarks of malignancy. Despite recent advances in the understanding of lymphatic spread, the mechanisms by which tumors metastasize to sentinel/distant lymph nodes and beyond are poorly understood. To gain new insights into this complex process, we established highly metastatic melanoma cell lines by in vivo passaging the B16 parental cell line through the lymphatic system. In this study we characterized morphology, rate of cell proliferation, colony f...

  2. Dose estimation in B16 tumour bearing mice for future irradiation in the thermal column of the TRIGA reactor after B/Gd/LDL adduct infusion

    Energy Technology Data Exchange (ETDEWEB)

    Protti, N., E-mail: nicoletta.protti@pv.infn.it [University of Pavia, Department of Nuclear and Theoretical Physics, via Bassi 6, 27100 Pavia (Italy)] [National Institute of Nuclear Physics (INFN) Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Ballarini, F.; Bortolussi, S. [University of Pavia, Department of Nuclear and Theoretical Physics, via Bassi 6, 27100 Pavia (Italy)] [National Institute of Nuclear Physics (INFN) Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Bruschi, P. [University of Pavia, Department of Nuclear and Theoretical Physics, via Bassi 6, 27100 Pavia (Italy); Stella, S. [University of Pavia, Department of Nuclear and Theoretical Physics, via Bassi 6, 27100 Pavia (Italy)] [National Institute of Nuclear Physics (INFN) Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Geninatti, S.; Alberti, D.; Aime, S. [University of Torino, Chemistry Department, via Nizza 52, 10126 Torino (Italy); Altieri, S. [University of Pavia, Department of Nuclear and Theoretical Physics, via Bassi 6, 27100 Pavia (Italy)] [National Institute of Nuclear Physics (INFN) Section of Pavia, via Bassi 6, 27100 Pavia (Italy)

    2011-12-15

    To test the efficacy of a new {sup 10}B-vector compound, the B/Gd/LDL adduct synthesised at Torino University, in vivo irradiations of murine tumours are in progress at the TRIGA Mark II reactor of the Pavia University. A localised B16 melanoma tumour is generated in C57BL/6 mice and subsequently infused with the adduct. During the irradiation, the mouse will be put in a shield to protect the whole body except the tumour in the back-neck area. To optimise the treatment set-up, MCNP simulations were performed. A very simplified mouse model was built using MCNP geometry capabilities, as well as the geometry of the shield made of 99% {sup 10}B enriched boric acid. A hole in the shield is foreseen in correspondence of the back-neck region. Many configurations of the shield were tested in terms of neutron flux, dose distribution and mean induced activity in the tumour region and in the radiosensitive organs of the mouse. In the final set-up, up to five mice can be treated simultaneously in the reactor thermal column and the neutron fluence in the tumour region for 10 min of irradiation is of about 5 Multiplication-Sign 10{sup 12} cm{sup -2}.

  3. Dose estimation in B16 tumour bearing mice for future irradiation in the thermal column of the TRIGA reactor after B/Gd/LDL adduct infusion.

    Science.gov (United States)

    Protti, N; Ballarini, F; Bortolussi, S; Bruschi, P; Stella, S; Geninatti, S; Alberti, D; Aime, S; Altieri, S

    2011-12-01

    To test the efficacy of a new (10)B-vector compound, the B/Gd/LDL adduct synthesised at Torino University, in vivo irradiations of murine tumours are in progress at the TRIGA Mark II reactor of the Pavia University. A localised B16 melanoma tumour is generated in C57BL/6 mice and subsequently infused with the adduct. During the irradiation, the mouse will be put in a shield to protect the whole body except the tumour in the back-neck area. To optimise the treatment set-up, MCNP simulations were performed. A very simplified mouse model was built using MCNP geometry capabilities, as well as the geometry of the shield made of 99% (10)B enriched boric acid. A hole in the shield is foreseen in correspondence of the back-neck region. Many configurations of the shield were tested in terms of neutron flux, dose distribution and mean induced activity in the tumour region and in the radiosensitive organs of the mouse. In the final set-up, up to five mice can be treated simultaneously in the reactor thermal column and the neutron fluence in the tumour region for 10 min of irradiation is of about 5×10(12) cm(-2). PMID:21459587

  4. Comparison of fusion cross sections for 10B + 16O and 12C + 14N systems

    International Nuclear Information System (INIS)

    The cross sections for fusion are compared for the 10B + 16O and 12C + 14N system for bombarding energies up to 17 MeV/A. The energy spectra, angular distribution and relative yields of the evaporation residues are extracted and, by comparison to simple kinematical analysis and Hauser-Feshbach calculations, it is concluded that they are consistent with complete fusion and equilibrium decay. Coincidence measurements for the 14N + 12C system at Esub(14N) = 182 MeV are also presented and confirm the identification of evaporation residues based on singles measurements of the Z distributions. The excitation functions for fusion for the 14N + 12C and 10B + 16O systems show significant differences that cannot be explained in terms of simple macroscopical models. For the highest energies studied the fusion cross sections decrease as 1/Esub(cm) for both systems, confirming the existence of a maximum absolute angular momentum limit of approximately 27h. (author)

  5. Characterization of melanoma associated spongiform scleropathy

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Heegaard, Steffen; Prause, J.U.

    ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology......ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology...

  6. Adenoviral vaccination combined with CD40 stimulation and CTLA-4 blockage can lead to complete tumor regression in a murine melanoma model

    DEFF Research Database (Denmark)

    Sørensen, Maria Rathmann; Holst, Peter J; Steffensen, Maria Abildgaard; Christensen, Jan P; Thomsen, Allan Randrup

    2010-01-01

    Therapeutic vaccination with replication deficient adenovirus expressing a viral antigen linked to invariant chain was recently found to markedly delay the growth of B16.F10 melanomas expressing the same antigen; however, complete regression of the tumors was never observed. Here we show that the...

  7. Proteomics in uveal melanoma.

    LENUS (Irish Health Repository)

    Ramasamy, Pathma

    2014-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.

  8. Melanoma International Foundation

    Science.gov (United States)

    ... 501(c)(3) charity, also registered as a non-profit charity in the state of Pennsylvania, certificate #29498 © 2013 Melanoma International Foundation. All Rights Reserved. Privacy Policy | Terms of Use ...

  9. Drugs Approved for Melanoma

    Science.gov (United States)

    ... are not listed here. Drugs Approved for Melanoma Aldesleukin Cobimetinib Cotellic (Cobimetinib) Dabrafenib Dacarbazine DTIC-Dome (Dacarbazine) IL-2 (Aldesleukin) Imlygic (Talimogene Laherparepvec) Interleukin-2 (Aldesleukin) Intron A ( ...

  10. Immunotherapy of Melanoma.

    Science.gov (United States)

    Snyder, Alexandra; Zamarin, Dmitriy; Wolchok, Jedd D

    2015-01-01

    The history of immunotherapy is rooted in the treatment of melanoma and therapy with immune checkpoint-blocking agents is now a cornerstone for the treatment of metastatic melanoma. The first effective immunotherapies approved by the US Food and Drug Administration in melanoma included interleukin-2 for metastatic disease and interferon alpha in the adjuvant setting. These were followed by a group of new therapies, including checkpoint-blocking antibodies targeting cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1. Therapies intended to 'reeducate' T cells, such as tumor-infiltrating lymphocyte therapy, oncolytic viruses and tumor vaccines, have yielded promising results and are under development. Finally, the integration of the above therapies as well as development of new coinhibitory and costimulatory agents, though in early stages, appear very promising and likely represent the next phase in drug development for the treatment of metastatic melanoma. PMID:26376963

  11. Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

    Science.gov (United States)

    2016-01-13

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  12. Pancreas Transplantation

    Science.gov (United States)

    ... by Mail Close www.diabetes.org > Living With Diabetes > Treatment and Care > Transplantation Share: Print Page Text Size: A A ... cc-kidneys-nephropathy, In this section Living With Diabetes Treatment and Care Transplantation Islet Transplantation Pancreas Transplantation Kidney Replacement Therapy ...

  13. Manganese-centered tubular boron cluster - MnB16-: A new class of transition-metal molecules

    Science.gov (United States)

    Jian, Tian; Li, Wan-Lu; Popov, Ivan A.; Lopez, Gary V.; Chen, Xin; Boldyrev, Alexander I.; Li, Jun; Wang, Lai-Sheng

    2016-04-01

    We report the observation of a manganese-centered tubular boron cluster (MnB16-), which is characterized by photoelectron spectroscopy and ab initio calculations. The relatively simple pattern of the photoelectron spectrum indicates the cluster to be highly symmetric. Ab initio calculations show that MnB16- has a Mn-centered tubular structure with C4v symmetry due to first-order Jahn-Teller effect, while neutral MnB16 reduces to C2v symmetry due to second-order Jahn-Teller effect. In MnB16-, two unpaired electrons are observed, one on the Mn 3dz2 orbital and another on the B16 tube, making it an unusual biradical. Strong covalent bonding is found between the Mn 3d orbitals and the B16 tube, which helps to stabilize the tubular structure. The current result suggests that there may exist a whole class of metal-stabilized tubular boron clusters. These metal-doped boron clusters provide a new bonding modality for transition metals, as well as a new avenue to design boron-based nanomaterials.

  14. Primary Anorectal Melanoma: An Update

    Directory of Open Access Journals (Sweden)

    P Carcoforo, M.T Raiji, G.M Palini, M Pedriali, U Maestroni, G Soliani, A Detroia, M.V Zanzi, A.L Manna, J.G Crompton, R.C Langan, A Stojadinovic, I Avital

    2012-01-01

    Full Text Available The anorectum is a rare anatomic location for primary melanoma. Mucosal melanoma is a distinct biological and clinical entity from the more common cutaneous melanoma. It portrays worse prognosis than cutaneous melanoma, with distant metastases being the overwhelming cause of morbidity and mortality. Surgery is the treatment of choice, but significant controversy exists over the extent of surgical resection. We present an update on the state of the art of anorectal mucosal melanoma. To illustrate the multimodality approach to anorectal melanoma, we present a typical patient.

  15. Antitumor effect of cytosine deaminase/5-fluorocytosine suicide gene therapy system mediated by Bifidobacterium infantis on melanoma

    Institute of Scientific and Technical Information of China (English)

    Cheng YI; Ying HUANG; Zhi-ying GUO; Shu-ren WANG

    2005-01-01

    Aim: To construct a Bifidobacterium infantis/CD targeting gene therapy system and observe the antitumor effect of cytosine deaminase/5-fluorocytosine (CD/5-FC) suicide gene therapy system mediated by Bifidobacterium infantis on melanoma in vitro and in vivo. Methods: A recombinant CD/pGEX- 1LamdaT plasmid was transfected into Bifidobacterium infantis by electroporation. Bifidobac terium infantis transfected by recombinant CD/pGEX-1LamdaT plasmid was in cubated with 5-FC anaerobically. Then the supernatant fluid was collected and added to melanoma B16-F10 cells to observe the killing effect for B16-F10 cells.Mice were inoculated with melanoma B 16-F10 cells to establish animal models.The mice were then injected with 5-FC and Bifidobacterium infantis transfected by recombinant CD/pGEX-1LamdaT plasmid. Results:Two segments of approxi mate 4.9 kb and 1.3 kb were extracted from the 6.2 kb recombinant plasmid, which were equal to the size of the pGEX-1LamdaT plasmid and CD gene, respectively.Sequencing results showed that the full length and sequence of nucleotide acid of the inserted gene in extracted recombinant plasmid was completely identical to the CD gene. In vitro, B 16-F10 cells treated by supernatant fluid were remarkably damaged morphologically, and the cell growth was significantly inhibited. Experi ments on the mice melanoma model showed that after treatment with a combination of transfected Bifidobacterium infantis and 5-FC, the tumor volume was significantly inhibited compared with controls. Conclusion: The foreign gene,CD gene, was correctly inserted into pGEX-1LambdaT plasmid and transferred into Bifidobacterium infantis. CD/5-FC suicide gene therapy system mediated by Bifidobacterium infantis demonstrated a good antitumor effect on melanoma in vitro and in vivo.

  16. Pancreatic transplantation

    Directory of Open Access Journals (Sweden)

    Åke Andrén-Sandberg

    2010-01-01

    Full Text Available A pancreas transplant is a surgical procedure to place a healthy pancreas from a donor into a patient whose pancreas no longer functions properly. Exocrine pancreas transplantation remains the standard treatment of choice for patients with diabetes mellitus complicated by end-stage renal disease. The use of pancreas transplantation for type 2 diabetes mellitus is an emerging concept. A pancreas transplant is often done in conjunction with a kidney transplant. Even if pancreas transplantation provides the best glycemic control option for diabetes mellitus, it is associated with significant morbidities related to infectious disease. The present article provides with a review of pancreatic transplantation.

  17. Biofunctional Activities of Equisetum ramosissimum Extract: Protective Effects against Oxidation, Melanoma, and Melanogenesis

    Science.gov (United States)

    Li, Pin-Hui; Chiu, Yu-Pin; Shih, Chieh-Chih; Wen, Zhi-Hong; Ibeto, Laura Kaodichi; Huang, Shu-Hung; Chiu, Chien Chih; Ma, Dik-Lung; Leung, Chung-Hang; Chang, Yaw-Nan; Wang, Hui-Min David

    2016-01-01

    Equisetum ramosissimum, a genus of Equisetaceae, is a medicinal plant that can be separated into ethyl acetate (EA), dichloromethane (DM), n-hexane (Hex), methanol (MeOH), and water extracts. EA extract was known to have potent antioxidative properties, reducing power, DPPH scavenging activity, and metal ion chelating activity. This study compared these five extracts in terms of their inhibiting effects on three human malignant melanomas: A375, A375.S2, and A2058. MTT assay presented the notion that both EA and DM extracts inhibited melanoma growth but did not affect the viabilities of normal dermal keratinocytes (HaCaT) or fibroblasts. Western blot analyses showed that both EA and DM extracts induced overexpression of caspase proteins in all three melanomas. To determine their roles in melanogenesis, this study analyzed their in vitro suppressive effects on mushroom tyrosinase. All extracts except for water revealed moderate suppressive effects. None of the extracts affected B16-F10 cells proliferation. EA extract inhibited cellular melanin production whereas DM extract unexpectedly enhanced cellular pigmentation in B16-F10 cells. Data for modulations of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2 showed that EA extract inhibited protein expression mentioned above whereas DM extract had the opposite effect. Overall, the experiments indicated that the biofunctional activities of EA extract contained in food and cosmetics protect against oxidation, melanoma, and melanin production. PMID:27403230

  18. Phenolic melanin precursors provide a rational approach to the design of antitumor agents for melanoma

    International Nuclear Information System (INIS)

    A unique biological property of the melanocyte, melanin synthesis may permit a rational approach to design agents for better management of malignant melanoma. This in vivo and in vitro study examined the selective melanocytotoxicity and antimelanoma effects of phenolic compounds, cysteinylphenol (CP), cysteaminylphenol (CAP), and related compounds, and found (1) that both 4-S-CP and 4-S-CAP are melanin precursors, (2) that 4-S-CAP possesses a marked depigmenting potency with selective destruction of melanocytes in black follicles, and (3) a significant inhibition in the protein synthesis and tumor growth of B16 melanoma. Importantly, a whole body autoradiography indicated that these phenolic melanin precursors are selectively incorporated into melanoma tissues after i.p. administration

  19. Melanoma targeting property of a Lu-177-labeled lactam bridge-cyclized alpha-MSH peptide

    OpenAIRE

    Guo, Haixun; Miao, Yubin

    2013-01-01

    The purpose of this study was to determine the melanoma targeting property of 177Lu-DOTA-GGNle-CycMSHhex in B16/F1 melanoma-bearing C57 mice. 177Lu-DOTA-GGNle-CycMSHhex exhibited high receptor-mediated melanoma uptake and fast urinary clearance. The tumor uptake of 177Lu-DOTA-GGNle-CycMSHhex was 20.25 ± 4.59 and 21.63 ± 6.27% ID/g at 0.5 and 2 h post-injection, respectively. Approximately 83% of injected dose cleared out the body via urinary system at 2 h post-injection. 177Lu-DOTA-GGNle-CycM...

  20. Recombinant E.coli LLO/OVA Vaccination Effectively Inhibits Murine Melanoma Metastasis to Lung by CD8+T Cells Immunity

    Institute of Scientific and Technical Information of China (English)

    Man Xu; Ming-shen Dai; Can Mi

    2009-01-01

    Objective: To construct recombinant E.coli LLO/OVA and investigate its tumor metastatic inhibition effect in B16 OVA melanoma challenged mice.Methods: Recombinant E.coli LLO/OVA was constructed and the expression of listeriolysin O (LLO) and ovalbumin (OVA) of the vaccine was determined by coomassie brilliant blue staining and western blotting. After 3 subcutaneous injections of E.coli LLO/OVA, the percentages of CD3+CD4+T, CD4+CD25+T, CD3+CD8+T and OVA257(264 SIINFEKL specific CD8+T cells were determined by flow cytomytry, and the tumor metastatic inhibition effect in B16 OVA melanoma challenged mice was observed.Results: Recombinant E.coli LLO/OVA was successfully constructed, and the expression of LLO and OVA of the vaccine was confirmed. After 3 subcutaneous injections of E.coli LLO/OVA and E.coli OVA in mice, the percentages of CD3+CD4+T, CD4+CD25+T and CD3+CD8+T cells were equivalent in the two groups of mice. However, there were significantly more OVA257(264 SIINFEKL specific CD8+T cells in E.coli LLO/OVA vaccinated mice than that in E.coli OVA vaccinated mice. The prophylactic E.coli LLO/OVA vaccination effectively prevented the tumor metastasis to lungs in B16 OVA melanoma challenged mice. Depletion of CD8+T cells significantly impaired the tumor inhibition effect of the vaccine in B16 OVA challenged mice. The therapeutic vaccination of E.coli LLO/OVA significantly prevented melanoma metastasis to lungs in B16 OVA challenged mice too.Conclusion: Recombinant E.coli LLO/OVA vaccination is highly effective in inhibiting murine malignant melanoma metastasis by promoting CD8+T cell immunity.

  1. Treatment Options by Stage (Melanoma)

    Science.gov (United States)

    ... of Skin Cancer Skin Cancer Screening Research Melanoma Treatment (PDQ®)–Patient Version General Information About Melanoma Key ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  2. Metastatic melanoma imaging with an 111In-labeled lactam bridge-cyclized α-melanocyte-stimulating hormone peptide

    International Nuclear Information System (INIS)

    Introduction: The purpose of this study was to examine whether a novel lactam bridge-cyclized 111In-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Gly-Glu-c[Lys-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-Asp] {DOTA-GlyGlu-CycMSH} could be an effective imaging probe for metastatic melanoma detection. Methods: 111In-DOTA-GlyGlu-CycMSH was prepared and purified by reverse-phase high-performance liquid chromatography (RP-HPLC). The internalization and efflux of 111In-DOTA-GlyGlu-CycMSH were examined in B16/F10 melanoma cells. The biodistribution of 111In-DOTA-GlyGlu-CycMSH was determined in B16/F10 pulmonary metastatic melanoma-bearing and normal C57 mice. Pulmonary metastatic melanoma imaging was performed by small-animal single-photon emission computed tomography (SPECT)/CT (Nano-SPECT/CT) using 111In-DOTA-GlyGlu-CycMSH as an imaging probe and compared with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) imaging. Results: 111In-DOTA-GlyGlu-CycMSH was readily prepared with greater than 95% radiolabeling yield. 111In-DOTA-GlyGlu-CycMSH displayed rapid internalization and extended efflux in B16/F10 cells. 111In-DOTA-GlyGlu-CycMSH exhibited significantly (P111In-DOTA-GlyGlu-CycMSH 2 h post-injection rather than with [18F]FDG 1 h post-injection. Conclusions: 111In-DOTA-GlyGlu-CycMSH exhibited favorable metastatic melanoma-targeting and -imaging properties, highlighting its potential as an effective imaging probe for metastatic melanoma detection.

  3. Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Thomas P Quinn

    2005-11-22

    -DOTA-Re(Arg11)CCMSH and {sup 212}Pb-DOTA-Re(Arg11)CCMSH complexes were developed and synthesized to investigate its ability to target and deliver an effective dose to small melanoma tumors and metastatic deposits. Dosimetry calculations for {sup 188}Re-CCMSH and {sup 212}Pb/{sup 212}Bi[DOTA]-Re(Arg11)CCMSH were compared in the B16/F1 mouse melanoma flank tumor model to analyze the delivered dose to tumor and normal organs.

  4. Gene transfer-applied BNCT (g-BNCT) for amelanotic melanoma in brain. Further upregulation of {sup 10}B uptake by cell modulation

    Energy Technology Data Exchange (ETDEWEB)

    Iwakura, M.; Tamaki, N. [Kobe Univ. (Japan). School of Medicine; Kondoh, H.; Mishima, Y. [Mishima Inst. for Dermatol. Res., Kobe, Hyogo (Japan); Hiratsuka, J. [Kawasaki Medical School, Dept. Radiation Oncol., Kurashiki, Okayama (Japan)

    2000-10-01

    Our success in eradicating melanoma by single BNCT with BPA led to the next urgent theme, i.e. application of such BNCT for currently uncurable melanoma metastasis in brain. In order to establish {sup 10}B-BPA-BNCT for melanoma in brain, we have investigated the pharmacokinetics of BPA which is most critical factor for successful BNCT, in melanotic and amelanotic and further tyrosinase gene-transfected amelanotic melanoma proliferating in brain having blood-brain-barrier, as compared to melanoma proliferating in skin. We have established three implanted models for melanoma in brain: 1) A1059 cells, amelanotic melanoma, 2) B16B15b cells, melanotic melanoma cells, highly metastatic to brain, and 3) TA1059 cells, with active melanogenesis induced by tyrosinase gene transfection. We would like to report the results of comparative analysis of the BPA uptake ability in these melanoma cells in both brain and skin. Based on these findings, we are further investigating to enhance {sup 10}B-BPA uptake by not only g-BNCT but also by additional melanogenesis upregulating cell modulation. (author)

  5. Gene transfer-applied BNCT (g-BNCT) for amelanotic melanoma in brain. Further upregulation of 10B uptake by cell modulation

    International Nuclear Information System (INIS)

    Our success in eradicating melanoma by single BNCT with BPA led to the next urgent theme, i.e. application of such BNCT for currently uncurable melanoma metastasis in brain. In order to establish 10B-BPA-BNCT for melanoma in brain, we have investigated the pharmacokinetics of BPA which is most critical factor for successful BNCT, in melanotic and amelanotic and further tyrosinase gene-transfected amelanotic melanoma proliferating in brain having blood-brain-barrier, as compared to melanoma proliferating in skin. We have established three implanted models for melanoma in brain: 1) A1059 cells, amelanotic melanoma, 2) B16B15b cells, melanotic melanoma cells, highly metastatic to brain, and 3) TA1059 cells, with active melanogenesis induced by tyrosinase gene transfection. We would like to report the results of comparative analysis of the BPA uptake ability in these melanoma cells in both brain and skin. Based on these findings, we are further investigating to enhance 10B-BPA uptake by not only g-BNCT but also by additional melanogenesis upregulating cell modulation. (author)

  6. Hair transplantation.

    Science.gov (United States)

    Avram, Marc R

    2012-12-01

    Hair transplantation is a purely dermatologic surgical procedure that dermatologists should be able to perform in appropriate candidates with hair loss. Hair transplantation techniques performed in the 1960s through the 1990s utilized large grafts that created an unfortunate public image of unnatural-appearing transplanted hair. Over the last 15 years, hair transplantation has been performed using follicular units to create consistently natural-looking transplanted hair in both men and women. This article provides an overview of candidate selection and state-of-the-art techniques for performing hair transplantation. PMID:23409484

  7. Metastatic melanoma imaging with an {sup 111}In-labeled lactam bridge-cyclized {alpha}-melanocyte-stimulating hormone peptide

    Energy Technology Data Exchange (ETDEWEB)

    Guo Haixun; Shenoy, Nalini; Gershman, Benjamin M.; Yang, Jianquan [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Sklar, Larry A. [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Pathology, University of New Mexico, Albuquerque, NM 87131 (United States); Miao Yubin [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Dermatology, University of New Mexico, Albuquerque, NM 87131 (United States)], E-mail: ymiao@salud.unm.edu

    2009-04-15

    Introduction: The purpose of this study was to examine whether a novel lactam bridge-cyclized {sup 111}In-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Gly-Glu-c[Lys-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Arg-Pro-Val-Asp] {l_brace}DOTA-GlyGlu-CycMSH{r_brace} could be an effective imaging probe for metastatic melanoma detection. Methods: {sup 111}In-DOTA-GlyGlu-CycMSH was prepared and purified by reverse-phase high-performance liquid chromatography (RP-HPLC). The internalization and efflux of {sup 111}In-DOTA-GlyGlu-CycMSH were examined in B16/F10 melanoma cells. The biodistribution of {sup 111}In-DOTA-GlyGlu-CycMSH was determined in B16/F10 pulmonary metastatic melanoma-bearing and normal C57 mice. Pulmonary metastatic melanoma imaging was performed by small-animal single-photon emission computed tomography (SPECT)/CT (Nano-SPECT/CT) using {sup 111}In-DOTA-GlyGlu-CycMSH as an imaging probe and compared with 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG) positron emission tomography (PET) imaging. Results: {sup 111}In-DOTA-GlyGlu-CycMSH was readily prepared with greater than 95% radiolabeling yield. {sup 111}In-DOTA-GlyGlu-CycMSH displayed rapid internalization and extended efflux in B16/F10 cells. {sup 111}In-DOTA-GlyGlu-CycMSH exhibited significantly (P<.05) higher uptakes (2.00{+-}0.74%ID/g at 2 h post-injection and 1.83{+-}0.12%ID/g at 4 h post-injection) in metastatic melanoma-bearing lung than that in normal lung (0.08{+-}0.08%ID/g and 0.05{+-}0.05%ID/g at 2 and 4 h post-injection, respectively). The activity accumulation in normal organs was low (<0.5%ID/g) except for the kidneys 2 and 4 h post-injection. B16/F10 pulmonary melanoma metastases were clearly visualized with {sup 111}In-DOTA-GlyGlu-CycMSH 2 h post-injection rather than with [{sup 18}F]FDG 1 h post-injection. Conclusions: {sup 111}In-DOTA-GlyGlu-CycMSH exhibited favorable metastatic melanoma-targeting and -imaging properties, highlighting its potential as an effective imaging

  8. Anti-melanogenic activity of the novel herbal medicine, MA128, through inhibition of tyrosinase activity mediated by the p38 mitogen-activated protein kinases and protein kinase signaling pathway in B16F10 cells

    Directory of Open Access Journals (Sweden)

    Aeyung Kim

    2014-01-01

    Full Text Available Background: Recently, our research group developed MA128, a novel herbal medicine, and demonstrated that MA128 is effective for the treatment of asthma and atopic dermatitis (AD. In particular, postinflammatory hyper-pigmentation in AD mice was improved with MA128 treatment. Thus, in this study, we determined the effect of MA128 on melanogenesis and its underlying mechanism in murine B16F10 melanoma cells. Materials and Methods: After treatment with MA128 at 100 and 250 μg/mL and/or alpha-melanocyte stimulating hormone (α-MSH (1 μM, cellular melanin content and tyrosinase activity in B16F10 cells were measured. Using western blotting, expression levels of tyrosinase, tyrosinase-related protein-1 (TRP-1, TRP-2, microphthalmia-associated transcription factor (MITF, and activation of c-AMP-dependent protein kinase (PKA, c-AMP-related element binding protein (CREB and mitogen-activated protein kinases (MAPKs were examined. Results: MA128 significantly inhibited melanin synthesis and tyrosinase activity in a resting state as well as α-MSH-stimulating condition, and significantly decreased the expression of tyrosinase, TRP-1, TRP-2 and MITF. In addition, phosphorylation of PKA and CREB by α-MSH stimulation was efficiently blocked by MA128 pretreatment. Moreover, MA128 as an herbal mixture showed synergistic anti-melanogenic effects compared with each single constituent herb. Conclusion: MA128 showed anti-melanogenic activity through inhibition of tyrosinase activity mediated by p38 MAPK and PKA signaling pathways in B16F10 cells. These results suggest that MA128 may be useful as an herbal medicine for controlling hyper-pigmentation and as a skin-whitening agent.

  9. Highly diluted compounds effects on B16-F10 melanogenesis, reactive oxygen species (ROS) production and tumorigenesis.

    OpenAIRE

    Edvaldo da Silva Trindade; Dorly de Freitas Buchi; Carolina Camargo Oliveira; Simone Martins de Oliveira; Helisa Wippel; Francine Bittencourt Potrich

    2012-01-01

    Background: Cutaneous melanoma is a highly malignant tumor derived from pigment-producing (melanin) melanocytes of skin epidermis. Cutaneous pigmentation is described as the major physiologic defense against UV radiation. During melanin biosynthesis and other tumorigenic process, reactive oxygen species (ROS) are produced and might be critically involved in several melanomagenesis stages. ROS play key roles on regulation of many types cell proliferation, including melanoma cells. Aims: In thi...

  10. Influence of rosmarinic acid and Salvia officinalis extracts on melanogenesis of B16F10 cells

    Directory of Open Access Journals (Sweden)

    Karina B. Oliveira

    2013-04-01

    Full Text Available Melanin is a photoprotective skin pigment, and pathologies characterized by hypo or hyperpigmentation are common. New compounds that regulate melanogenesis are, therefore, opportune, and many natural products with this property, as polyphenols, have been described. Salvia officinalis L., Lamiaceae, is a widely used food spice that contains high amounts of phenol derivates, including rosmarinic acid. The aim of this work was to evaluate the contribution of rosmarinic acid in the melanogenic activity of sage extracts. Fluid and aqueous extracts of sage and purified rosmarinic acid were assayed for B16F10 cytotoxicity and, then, evaluated on melanin production and tyrosinase activity. While sage extracts showed a concentration-dependent ability to significantly increase melanin production without necessarily changing the enzymatic activity, rosmarinic acid showed a dual behavior on melanogenesis, increasing melanin biosynthesis and tyrosinase activity at low concentrations and decreasing it at higher levels. Rosmarinic acid may collaborate with sage extracts activity on melanogenesis, although other compounds may be involved. This is the first time that a dual action of rosmarinic acid on melanogenesis is reported, which may be useful in further studies for therapeutic formulations to treat skin pigmentation disorders.

  11. Influence of rosmarinic acid and Salvia officinalis extracts on melanogenesis of B16F10 cells

    Directory of Open Access Journals (Sweden)

    Karina B. Oliveira

    2012-01-01

    Full Text Available Melanin is a photoprotective skin pigment, and pathologies characterized by hypo or hyperpigmentation are common. New compounds that regulate melanogenesis are, therefore, opportune, and many natural products with this property, as polyphenols, have been described. Salvia officinalis L., Lamiaceae, is a widely used food spice that contains high amounts of phenol derivates, including rosmarinic acid. The aim of this work was to evaluate the contribution of rosmarinic acid in the melanogenic activity of sage extracts. Fluid and aqueous extracts of sage and purified rosmarinic acid were assayed for B16F10 cytotoxicity and, then, evaluated on melanin production and tyrosinase activity. While sage extracts showed a concentration-dependent ability to significantly increase melanin production without necessarily changing the enzymatic activity, rosmarinic acid showed a dual behavior on melanogenesis, increasing melanin biosynthesis and tyrosinase activity at low concentrations and decreasing it at higher levels. Rosmarinic acid may collaborate with sage extracts activity on melanogenesis, although other compounds may be involved. This is the first time that a dual action of rosmarinic acid on melanogenesis is reported, which may be useful in further studies for therapeutic formulations to treat skin pigmentation disorders.

  12. Transplant services

    Science.gov (United States)

    ... the eye on which a contact lens rests. Heart transplant is an option for someone with congestive heart ... treat all medical problems, such as kidney and heart disease. The transplant team will evaluate you and review your medical ...

  13. Heart Transplant

    Science.gov (United States)

    ... 2015 A heart transplant gives a patient with congenital heart disease the opportunity to have a normal heart with ... pulmonary artery and left atrium. In patients with congenital heart disease, the surgeon may simultaneous transplant the lungs and ...

  14. Intestine Transplant

    Science.gov (United States)

    ... Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Intestine Transplant Although it is possible for a living donor to donate an intestine segment, most intestine transplants involve a whole organ ...

  15. Heart Transplantation

    Science.gov (United States)

    A heart transplant removes a damaged or diseased heart and replaces it with a healthy one. The healthy heart comes ... defects, or viral infections of the heart. Although heart transplant surgery is a life-saving measure, it has ...

  16. Pancreas transplant

    Science.gov (United States)

    ... worse and may even improve after a pancreas-kidney transplant. More than 95% of people survive the first year after a pancreas transplant. Organ rejection occurs in about 1% of people each year. ...

  17. Stimulation of lymphocyte anti-melanoma activity by co-cultured macrophages activated by complex homeopathic medication

    International Nuclear Information System (INIS)

    Melanoma is the most aggressive form of skin cancer, and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have been uniformly disappointing. A Brazilian complex homeopathic medication (CHM), used as an immune modulator, has been recommended for patients with depressed immune systems. Previous studies in mice have demonstrated that the CHM activates macrophages, induces an increase in the number of leukocytes and improves the murine response against Sarcoma-180. Here we studied the interaction of mouse lymph node lymphocytes, co-cultured in vitro with macrophages in the presence or absence of the CHM, with B16F10 melanoma cells. Lymphocytes co-cultured with macrophages in the presence of the CHM had greater anti-melanoma activity, reducing melanoma cell density and increasing the number of lysed tumor cells. There was also a higher proportion of activated (CD25+) lymphocytes with increased viability. Overall, lymphocytes activated by treatment destroyed growing cancer cells more effectively than control lymphocytes. Co-culture of macrophages with lymphocytes in the presence of the CHM enhanced the anti-cancer performance of lymphocytes against a very aggressive lineage of melanoma cells. These results suggest that non-toxic therapies using CHMs are a promising alternative approach to the treatment of melanomas. In addition, they are attractive combination-therapy candidates, which may enhance the efficacy of conventional medicines by improving the immune response against tumor cells

  18. Effective melanoma immunotherapy in mice by the skin-depigmenting agent monobenzone and the adjuvants imiquimod and CpG.

    Directory of Open Access Journals (Sweden)

    Jasper G van den Boorn

    Full Text Available BACKGROUND: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity. METHODOLOGY AND PRINCIPAL FINDINGS: We developed an effective and simple to use form of immunotherapy by combining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides (CpG injections (MIC therapy. This powerful new approach promptly induced a melanoma antigen-specific immune response, which abolished subcutaneous B16.F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly, this regimen induced over 100 days of tumor-free survival in up to 60% of the mice, and forcefully suppressed tumor growth upon re-challenge either 65- or 165 days after MIC treatment cessation. CONCLUSIONS: MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B- and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple therapy, readily applicable in the clinic.

  19. Melanoma of the Foot.

    Science.gov (United States)

    Bristow, Ivan; Bower, Chris

    2016-07-01

    Melanoma is a rare form of skin cancer that is responsible for most skin cancer deaths globally. Tumors arising on the foot continue to be a particular challenge. Patients present later and lesions are frequently misdiagnosed, leading to more advanced disease with an overall poorer prognosis then melanoma elsewhere. In order to improve early recognition, this article reviews the clinical features of the disease along with published algorithms. Emerging assessment techniques such as dermoscopy are also discussed as tools to improve clinical decision making. Contemporary drug therapies in the treatment of advanced disease are also discussed. PMID:27215160

  20. Angiogenesis and Melanoma

    International Nuclear Information System (INIS)

    Angiogenesis occurs in pathological conditions, such as tumors, where a specific critical point in tumor progression is the transition from the avascular to the vascular phase. Tumor angiogenesis depends mainly on the release by neoplastic cells of growth factors specific for endothelial cells, which are able to stimulate the growth of the host’s blood vessels. This article summarizes the literature concerning the relationship between angiogenesis and human melanoma progression. The recent applications of antiangiogenic agents which interfere with melanoma progression are also described

  1. Vitamins and Melanoma

    Directory of Open Access Journals (Sweden)

    Irene Russo

    2015-07-01

    Full Text Available A tremendous amount of information was published over the past decades in relation to the role of vitamins in various neoplastic diseases. In particular, several studies showed an inverse relationship between selected vitamins intake and cancer risk. In this review we will focus on the role played by vitamins in melanoma with particular regard to vitamin A, D, K, E and C. Given that vitamin supplementation is easy, convenient, and readily accepted by patients, in the future the use of vitamins in chemoprevention and therapy of melanoma could be encouraged if supported by pre-clinical and clinical evidence.

  2. Organ Transplantation

    Science.gov (United States)

    ... organs that can be transplanted include Heart Intestine Kidney Liver Lung Pancreas You often have to wait a long time for an organ transplant. Doctors must match donors to recipients to reduce the risk of transplant rejection. Rejection happens when your immune system attacks the ...

  3. Let-7b-mediated suppression of basigin expression and metastasis in mouse melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Tzu-Yen [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Chang, Chia-Che [Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, 91 Hsueh Shih Road, Taichung 40402, Taiwan (China); Lin, Chun-Ting [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Lai, Cong-Hao [Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Department of Life Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Peng, Shao-Yu; Ko, Yi-Ju [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China); Tang, Pin-Chi, E-mail: pctang@dragon.nchu.edu.tw [Department of Animal Science, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan (China)

    2011-02-15

    Basigin (Bsg), also called extracellular matrix metalloproteinase inducer (EMMPRIN), is highly expressed on the surface of tumor cells and stimulates adjacent fibroblasts or tumor cells to produce matrix metalloproteinases (mmps). It has been shown that Bsg plays an important role in growth, development, cell differentiation, and tumor progression. MicroRNAs (miRNAs) are a class of short endogenous non-protein coding RNAs of 20-25 nucleotides (nt) that function as post-transcriptional regulators of gene expression by base-pairing to their target mRNAs and thereby mediate cleavage of target mRNAs or translational repression. In this study, let-7b, one of the let-7 family members, was investigated for its effect on the growth and invasiveness of the mouse melanoma cell line B16-F10. We have shown that let-7b can suppress the expression of Bsg in B16-F10 cells and also provided evidence that this suppression could result in the indirect suppression of mmp-9. The ability of B16-F10 cells transfected with let-7b to invade or migrate was significantly reduced. In addition, let-7b transfected B16-F10 cells displayed an inhibition of both cellular proliferation and colony formation. Furthermore, it was shown that the overexpression of let-7b in B16-F10 cells could reduce lung metastasis. Taken together, the present study identifies let-7b as a tumor suppressor that represses cancer cell proliferation and migration as well as tumor metastasis in mouse melanoma cells.

  4. The regional genomic instability induced by 60Co γ-rays in B16 cells transfected by GFP

    International Nuclear Information System (INIS)

    Objective: To detect the regional genomic instability of B16 cells treated with 60Co γ-rays by a green fluorescence protein (GFP)-based genomic instability reporting system. Methods: Three groups were employed as non-transfection group, vector control group and transfection group. The GFP-marked reporter construct pCMV-EGFP2XhoI for regional genomic instability was successfully transfected into B16 cells using liposome. B16 cells were selected by screening of G418 with a series of concentrations and limiting dilution cultures to yield a single colony. B16 cells with the genomic instability report system were then irradiated by 60Co γ-rays at doses of 0, 2 and 4 Gy. The regional genomic instability of B16 cells was quantified by counting the number of cells with GFP expression. Results: B-16 cell strain steadily expressing the GFP-based genomic instability reporting system was established successfully. GFP-positive B16 cells were observed at 1 d after irradiation with 60Co γ-rays at doses of 2 and 4 Gy. Positive correlations between fluorescence intensity and dose and fluorescence intensity and time were also observed. The positive expression rate of GFP followed the increased of dose (F=36.55, 36.76, P<0.05) and time (t=-3.27, -3.16, -4.26, -6.11, -7.17, P<0.05), and differences between groups were significant. The positive expression rate of GFP increased significantly at 3 d, and maximum expression was observed at 5 d (2.46 ± 0.24 and 3.82 ± 0.35). The level was tending towards stability. Spontaneous GFP expression at a ratio of 1/600000 was observed in 0 Gy group after 2 weeks of culture. Conclusions: The regional genomic instability of B16 cells induced by 60Co γ-rays can be detected using a GFP-labelled genomic instability reporter system. (authors)

  5. Inhibition of B16BL6 tumor progression by coadministration of recombinant angiostatin K1-3 and endostatin genes with cationic liposomes.

    Science.gov (United States)

    Kim, Keun Sik; Kim, Hong Sung; Park, Jin Seu; Kwon, Young Guen; Park, Yong Serk

    2004-06-01

    Transfection of the antiangiogenic angiostatin and endostatin genes was shown to be an alternative to high-dose administration of angiostatin or endostatin proteins for cancer therapy. We have systematically investigated whether coadministration of the mouse angiostatin kringle 1-3 gene (pFLAG-AngioK1/3) and the endostatin gene (pFLAG-Endo) complexed with cationic liposomes exhibits enhanced therapeutic efficacy. In vitro, the coexpressed mixture of angiostatin K1-3 and endostatin more effectively reduced angiogenesis in chorioallantoic membranes than either angiostatin K1-3 or endostatin alone. In vivo, subcutaneous co-administration of pFLAG-AngioK1/3 and pFLAG-Endo lipoplexes more effectively inhibited vascularization in Matrigel plugs implanted in mice than either one alone. Additionally, subcutaneous administration of these genes inhibited the growth and formation of pulmonary metastases of B16BL6 melanoma cells in mice. Compared to treatment with an empty vector, treatment with pFLAG-AngioK1/3 plus pFLAG-Endo inhibited 81% of tumor growth, while treatment with pFLAG-AngioK1/3 or pFLAG-Endo inhibited tumor growth 70 and 69%, respectively. Cotreatment with the two plasmids after primary tumor excision induced a 90% inhibition of pulmonary metastases versus 79% for pFLAG-AngioK1/3 or 80% for pFLAG-Endo individually. These results suggest that combined administration of angiostatin K1-3 and endostatin genes complexed with cationic liposomes may be an innovated antiangiogenic strategy for cancer therapy. PMID:15118757

  6. Magnetic and thermal behaviour of the amorphous ferromagnet Fe79B16Si5

    International Nuclear Information System (INIS)

    Spin waves in the amorphous ferromagnet Fe79B16Si5 are studied by Moessbauer effect spectroscopy. The magnetic hyperfine field (MHF) is measured at the Fe sites of such a ferromagnet, which exhibits a temperature dependence of the form, H(T)/H(0) = (1 - BT/sup 3/2/ - CT/sup 5/2/), indicative of spin wave excitations in amorphous ferromagnets. The T/sup 3/2/ behaviour and the distribution of the exchange interactions are studied in detail as a function of the MHF. The spin wave excitations constant B/sub 3/2/ = BT/sub C//sup 3/2/ = 0.3 +- 0.05 and C/sub 5/2/ = CT/sub C//sup 5/2/ = 0.3 +- 0.05,Are obtained by fitting the experimental data, and where T/sub C/ = 670 K. The results sh=ow that the contribution of C/sub 5/2/ is extremely effective above 124 K, while the ratio C/sub 5/2//C/sub 3/2/ = 1.0 indicates that the present magnetic interaction is of long range order character. On the other hand, fluctuations of the exchange interaction constant are found to decrease with increasing temperature. Some information regarding the directions of the magnetic moments are obtained during the study of the magnetic anisotropy course. The values of the Einstein and Debye temperatures as measured from the thermal shift results are theta/sub E/ = 250 K and theta/sub D/ = 350 K,And from the Moessbauer factor measurements theta/sub E/ = 165 K and theta/sub D/ = 285 K. (autho=r)

  7. Melanoma Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing melanoma cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  8. Spice Blocks Melanoma Growth

    Science.gov (United States)

    Science Teacher, 2005

    2005-01-01

    Curcumin, the pungent yellow spice found in both turmeric and curry powders, blocks a key biological pathway needed for development of melanoma and other cancers, according to a study that appears in the journal Cancer. Researchers from The University of Texas M. D. Anderson Cancer Center demonstrate how curcumin stops laboratory strains of…

  9. Malignant melanoma of nose

    OpenAIRE

    Kundu, I. N.; Haldar, B.; Saha, A. K.

    2001-01-01

    Malignant melanoma (MM) is one of the uncommon malignancies of the nose. We present an unusually big proliferative like MM in the vestibule of the nose. Malignancy of nose constitutes less than 1% of all malignancies (3% of head & neck tumour). MM however contributes only 2% of all malignant neoplasms of the nose (Moore & Martin. 1955).

  10. Melanoma risk prediction models

    Directory of Open Access Journals (Sweden)

    Nikolić Jelena

    2014-01-01

    Full Text Available Background/Aim. The lack of effective therapy for advanced stages of melanoma emphasizes the importance of preventive measures and screenings of population at risk. Identifying individuals at high risk should allow targeted screenings and follow-up involving those who would benefit most. The aim of this study was to identify most significant factors for melanoma prediction in our population and to create prognostic models for identification and differentiation of individuals at risk. Methods. This case-control study included 697 participants (341 patients and 356 controls that underwent extensive interview and skin examination in order to check risk factors for melanoma. Pairwise univariate statistical comparison was used for the coarse selection of the most significant risk factors. These factors were fed into logistic regression (LR and alternating decision trees (ADT prognostic models that were assessed for their usefulness in identification of patients at risk to develop melanoma. Validation of the LR model was done by Hosmer and Lemeshow test, whereas the ADT was validated by 10-fold cross-validation. The achieved sensitivity, specificity, accuracy and AUC for both models were calculated. The melanoma risk score (MRS based on the outcome of the LR model was presented. Results. The LR model showed that the following risk factors were associated with melanoma: sunbeds (OR = 4.018; 95% CI 1.724- 9.366 for those that sometimes used sunbeds, solar damage of the skin (OR = 8.274; 95% CI 2.661-25.730 for those with severe solar damage, hair color (OR = 3.222; 95% CI 1.984-5.231 for light brown/blond hair, the number of common naevi (over 100 naevi had OR = 3.57; 95% CI 1.427-8.931, the number of dysplastic naevi (from 1 to 10 dysplastic naevi OR was 2.672; 95% CI 1.572-4.540; for more than 10 naevi OR was 6.487; 95%; CI 1.993-21.119, Fitzpatricks phototype and the presence of congenital naevi. Red hair, phototype I and large congenital naevi were

  11. Immune-mediated regression of established B16F10 melanoma by intratumoral injection of attenuated Toxoplasma gondii protects against rechallenge

    OpenAIRE

    Baird, Jason R; Byrne, Katelyn T.; Lizotte, Patrick H; Toraya-Brown, Seiko; Scarlett, Uciane K.; Alexander, Matthew P.; Sheen, Mee Rie; Fox, Barbara A.; Bzik, David J.; Bosenberg, Marcus; Mullins, David W.; Turk, Mary Jo; Fiering, Steven

    2012-01-01

    Immune recognition of tumors can limit cancer development, but antitumor immune responses are often blocked by tumor-mediated immunosuppression. Since microbes or microbial constituents are powerful adjuvants to stimulate immune responses, we evaluated whether intratumoral administration of a highly immunogenic but attenuated parasite could induce rejection of an established poorly immunogenic tumor.

  12. Antitumor activity of N-acetyl-D-glucosamine-substituted glycoconjugates and combined therapy with keyhole limpet hemocyanin in B16F10 mouse melanoma model

    Czech Academy of Sciences Publication Activity Database

    Huliková, Katarína; Grobárová, Valeria; Křivohlavá, Romana; Fišerová, Anna

    2010-01-01

    Roč. 55, č. 5 (2010), s. 528-532. ISSN 0015-5632 R&D Projects: GA AV ČR IAA500200620; GA AV ČR IAA601680801; GA ČR GD310/08/H077 Institutional research plan: CEZ:AV0Z50200510 Keywords : IN-VIVO * CYTOTOXICITY * LIGANDS Subject RIV: EC - Immunology Impact factor: 0.977, year: 2010

  13. Down-regulation of tyrosinase, TRP-1, TRP-2 and MITF expressions by citrus press-cakes in murine B16 F10 melanoma

    Institute of Scientific and Technical Information of China (English)

    Sang Suk Kim; Min-Jin Kim; Young Hun Choi; Byung Kuk Kim; Kwang Sik Kim; Kyung Jin Park; Suk Man Park; Nam Ho Lee; Chang-Gu Hyun

    2013-01-01

    Objective: To investigate the suitability of citrus-press cakes, by-products of the juice industry as a source for the whitening agents for cosmetic industry. Methods:Ethylacetate extracts of citrus-press cakes (CCE) were examined for their anti-melanogenic potentials in terms of the inhibition of melanin production and mechanisim of melanogenesis by using Western Blot analysis with tyrosinese, tyrosinase-related protein-1 (TRP-1), TRP2, and microphthalmia-associated transcription factor (MITF) proteins. To apply the topical agents, citrus-press cakes was investigated the safety in human skin cell line. Finally flavonoid analysis of CCE was also determined by HPLC analysis. Results: Results indicated that CCE were shown to down-regulate melanin content in a dose-dependent pattern. The CCE inhibited tyrosinase, TRP-2, and MITF expressions in a dose-dependent manner. To test the applicability of CCE to human skin, we used MTT assay to assess the cytotoxic effects of CCE on human keratinocyte HaCaT cells. The CCE exhibited low cytotoxicity at 50 µg/mL. Characterization of the citrus-press cakes for flavonoid contents using HPLC showed varied quantity of rutin, narirutin, and hesperidin. Conclusions:Considering the anti-melanogenic activity and human safety, CCE is considered as a potential anti-melanogenic agent and may be effective for topical application for treating hyperpigmentation disorders.

  14. Effect of N-acetyl-glucosamine-coated glycodendrimers as biological modulators in the B16F10 melanoma model is vivo

    Czech Academy of Sciences Publication Activity Database

    Vannucci, Luca; Fišerová, Anna; Sadalapure, K.; Lindhorst, T.; Kuldová, Miloslava; Rossmann, Pavel; Horváth, Ondřej; Křen, Vladimír; Krist, Pavel; Bezouška, Karel

    2003-01-01

    Roč. 23, - (2003), s. 285-296. ISSN 1019-6439 Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z5020903 Keywords : carbohydrates * dendrimers * lectin-like Subject RIV: EE - Microbiology, Virology Impact factor: 2.536, year: 2003

  15. Comparative Depigmentation Effects of Resveratrol and Its Two Methyl Analogues in α-Melanocyte Stimulating Hormone-Triggered B16/F10 Murine Melanoma Cells

    OpenAIRE

    Yoon, Hoon-Seok; Hyun, Chang-Gu; Lee, Nam-Ho; Park, Sung-Soo; Shin, Dong-Bum

    2016-01-01

    Previous research showed that resveratrol (trans-3,4′,5-trihydroxystilbene) and pinostilbene (trans-3-methoxy-4′,5-dihydroxystilbene) were able to inhibit tyrosinase directly; however, anti-melanogenic effects of pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene) and resveratrol trimethyl ether (RTE) have not been compared. To investigate the hypopigmentation effects of pterostilbene and RTE, melanin contents and intracellular tyrosinase activity were determined by western blot analysis. ...

  16. Penurunan Aktivitas Tirosinase dan Jumlah Melanin oleh Fraksi Etil Asetat Buah Malaka (Phyllantus emblica) pada Mouse Melanoma B16 Cell-Line

    OpenAIRE

    Reti Hindritiani; Diah Dhianawaty; Muchtan Sujatno; Endang Sutedja; Setiawan

    2013-01-01

    Melanin accumulation can lead to hyperpigmentation, and if it occurs on the face can cause psychosocial problem. Depigmenting agents derived from plants are increasingly utilized. Agents being developed have to be effective in inhibiting melanin synthesis and should not be toxic to melanocyte. This study aimed was to examine the effect of ethyl acetate fraction from Phyllanthus emblica (P. emblica) fruit, also known as malaka fruit, towards melanine synthesis, which was measured from the mela...

  17. 75 FR 59071 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B16 (CL-604 Variants (Including CL-605...

    Science.gov (United States)

    2010-09-27

    ... in the Federal Register on June 2, 2010 (75 FR 30740). That NPRM proposed to correct an unsafe...'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will not have.... Model CL-600-2B16 (CL- 604 Variants (Including CL-605 Marketing Variant)) Airplanes AGENCY:...

  18. 75 FR 38011 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B16 (CL-604 Variant) Airplanes

    Science.gov (United States)

    2010-07-01

    ... products. That NPRM was published in the Federal Register on January 4, 2010 (75 FR 91). That NPRM proposed... Order 12866; 2. Is not a ``significant rule'' under the DOT Regulatory Policies and Procedures (44 FR.... Model CL-600-2B16 (CL- 604 Variant) Airplanes AGENCY: Federal Aviation Administration (FAA),...

  19. 75 FR 30740 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B16 (CL-604 Variants (Including CL-605...

    Science.gov (United States)

    2010-06-02

    ... Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant economic impact, positive or... Directives; Bombardier, Inc. Model CL-600-2B16 (CL- 604 Variants (Including CL-605 Marketing Variant... addition to Bombardier Inc. Models CL-600-2B19, CL-600-2C10 and CL-600-2D24. The latter three models...

  20. Melanoma inhibitor of apoptosis protein is expressed differentially in melanoma and melanocytic naevus, but similarly in primary and metastatic melanomas

    OpenAIRE

    Gong, J; Chen, N; Zhou, Q; Yang, B.; Wang, Y; Wang, X.

    2005-01-01

    Background: Malignant melanoma is highly resistant to current treatments. The inhibitor of apoptosis protein (IAP) family member, melanoma IAP (ML-IAP), is overexpressed in some melanoma cell lines, rendering them resistant to apoptotic signals. Targeting ML-IAP is a promising approach to treating melanoma. However, the status of ML-IAP expression in human melanoma tissues and the difference in expression between melanoma and melanocytic naevus are not known.

  1. NAADP-Dependent Ca(2+) Signaling Controls Melanoma Progression, Metastatic Dissemination and Neoangiogenesis.

    Science.gov (United States)

    Favia, Annarita; Pafumi, Irene; Desideri, Marianna; Padula, Fabrizio; Montesano, Camilla; Passeri, Daniela; Nicoletti, Carmine; Orlandi, Augusto; Del Bufalo, Donatella; Sergi, Manuel; Ziparo, Elio; Palombi, Fioretta; Filippini, Antonio

    2016-01-01

    A novel transduction pathway for the powerful angiogenic factor VEGF has been recently shown in endothelial cells to operate through NAADP-controlled intracellular release of Ca(2+). In the present report the possible involvement of NAADP-controlled Ca(2+) signaling in tumor vascularization, growth and metastatic dissemination was investigated in a murine model of VEGF-secreting melanoma. Mice implanted with B16 melanoma cells were treated with NAADP inhibitor Ned-19 every second day for 4 weeks and tumor growth, vascularization and metastatization were evaluated. Control specimens developed well vascularized tumors and lung metastases, whereas in Ned-19-treated mice tumor growth and vascularization as well as lung metastases were strongly inhibited. In vitro experiments showed that Ned-19 treatment controls the growth of B16 cells in vitro, their migratory ability, adhesive properties and VEGFR2 expression, indicating NAADP involvement in intercellular autocrine signaling. To this regard, Ca(2+) imaging experiments showed that the response of B16 cells to VEGF stimulation is NAADP-dependent. The whole of these observations indicate that NAADP-controlled Ca(2+) signaling can be relevant not only for neoangiogenesis but also for direct control of tumor cells. PMID:26733361

  2. NAADP-Dependent Ca2+ Signaling Controls Melanoma Progression, Metastatic Dissemination and Neoangiogenesis

    Science.gov (United States)

    Favia, Annarita; Pafumi, Irene; Desideri, Marianna; Padula, Fabrizio; Montesano, Camilla; Passeri, Daniela; Nicoletti, Carmine; Orlandi, Augusto; Del Bufalo, Donatella; Sergi, Manuel; Ziparo, Elio; Palombi, Fioretta; Filippini, Antonio

    2016-01-01

    A novel transduction pathway for the powerful angiogenic factor VEGF has been recently shown in endothelial cells to operate through NAADP-controlled intracellular release of Ca2+. In the present report the possible involvement of NAADP-controlled Ca2+ signaling in tumor vascularization, growth and metastatic dissemination was investigated in a murine model of VEGF-secreting melanoma. Mice implanted with B16 melanoma cells were treated with NAADP inhibitor Ned-19 every second day for 4 weeks and tumor growth, vascularization and metastatization were evaluated. Control specimens developed well vascularized tumors and lung metastases, whereas in Ned-19-treated mice tumor growth and vascularization as well as lung metastases were strongly inhibited. In vitro experiments showed that Ned-19 treatment controls the growth of B16 cells in vitro, their migratory ability, adhesive properties and VEGFR2 expression, indicating NAADP involvement in intercellular autocrine signaling. To this regard, Ca2+ imaging experiments showed that the response of B16 cells to VEGF stimulation is NAADP-dependent. The whole of these observations indicate that NAADP-controlled Ca2+ signaling can be relevant not only for neoangiogenesis but also for direct control of tumor cells. PMID:26733361

  3. Dehydroleucodine inhibits tumor growth in a preclinical melanoma model by inducing cell cycle arrest, senescence and apoptosis.

    Science.gov (United States)

    Costantino, Valeria V; Lobos-Gonzalez, Lorena; Ibañez, Jorge; Fernandez, Dario; Cuello-Carrión, F Darío; Valenzuela, Manuel A; Barbieri, Manuel A; Semino, Silvana N; Jahn, Graciela A; Quest, Andrew F G; Lopez, Luis A

    2016-03-01

    Malignant melanoma represents the fastest growing public health risk of all cancer types worldwide. Several strategies and anti-cancer drugs have been used in an effort to improve treatments, but the development of resistance to anti-neoplastic drugs remains the major cause of chemotherapy failure in melanomas. Previously, we showed that the sesquiterpene lactone, dehydroleucodine (DhL), promotes the accumulation of DNA damage markers, such as H2AX and 53BP1, in human tumor cells. Also DhL was shown to trigger either cell senescence or apoptosis in a concentration-dependent manner in HeLa and MCF7 cells. Here, we evaluated the effects of DhL on B16F0 mouse melanoma cells in vitro and in a pre-clinical melanoma model. DhL inhibited the proliferation of B16F0 cells by inducing senescence or apoptosis in a concentration-dependent manner. Also, DhL reduced the expression of the cell cycle proteins cyclin D1 and B1 and the inhibitor of apoptosis protein, survivin. In melanomas generated by subcutaneous injection of B16F0 cells into C57/BL6 mice, the treatment with 20 mg DhL /Kg/day in preventive, simultaneous and therapeutic protocols reduced tumor volumes by 70%, 60% and 50%, respectively. DhL treatments reduced the number of proliferating, while increasing the number of senescent and apoptotic tumor cells. To estimate the long-term effects of DhL, a mathematical model was applied to fit experimental data. Extrapolation beyond experimental time points revealed that DhL administration following preventive and therapeutic protocols is predicted to be more effective than simultaneous treatments with DhL in restricting tumor growth. PMID:26718258

  4. Characterization of the melanoma brain metastatic niche in mice and humans

    International Nuclear Information System (INIS)

    Brain metastases occur in 15% of patients with melanoma and are associated with a dismal prognosis. Here, we investigate the architectural phenotype and stromal reaction of melanoma brain metastasis in mice and humans. A syngeneic, green fluorescence protein (GFP)-expressing murine B16-F1 melanoma clone was introduced via intracardiac injection, and was examined in vivo in comparison with human specimens. Immunofluorescence analyses of the brain metastases revealed that F4/80+ macrophages/microglia were most abundant at the tumor front, but rare in its core, where they were found only around blood vessels (P = 0.01). Similar pattern of infiltration was found in CD3+ T cells (P < 0.01). Infiltrating T cells were prominently CD4+ compared with CD8+ T cells (P < 0.001). Blood vessels (CD31+) were less abundant at the tumor front than in its center (12 ± 1 vs. 4 ± 0.6 vessels per high-power field [HPF], P < 0.001). In contrast, there were few vessels at the tumor front, but their diameter was significantly larger at the front (8236 μm2 vs. 4617 μm2 average cross-sectional area, P < 0.005). This is the first comparative analysis of melanoma brain metastases showing similar stromal reaction in murine models and human specimens. Our results validate the utility of this murine model of melanoma brain metastases for investigating the mechanism of the human disease

  5. Primary glandular melanoma of male breast with nodal metastasis

    OpenAIRE

    Jayabal Pandiaraja

    2016-01-01

    Malignant melanoma is a malignancy that develops from melanocytes. Breast is an uncommon site for malignant melanoma. Melanoma of the breast occurs in various situations such as primary melanoma of breast skin, metastatic melanoma of breast, in-transit metastasis to the breast, and primary glandular breast melanoma. Most of the melanoma breast either cutaneous melanoma or metastatic melanoma. Primary glandular melanoma of male breast with nodal involvement is rarely reported compared to prima...

  6. Direct Melanoma Cell Contact Induces Stromal Cell Autocrine Prostaglandin E2-EP4 Receptor Signaling That Drives Tumor Growth, Angiogenesis, and Metastasis.

    Science.gov (United States)

    Inada, Masaki; Takita, Morichika; Yokoyama, Satoshi; Watanabe, Kenta; Tominari, Tsukasa; Matsumoto, Chiho; Hirata, Michiko; Maru, Yoshiro; Maruyama, Takayuki; Sugimoto, Yukihiko; Narumiya, Shuh; Uematsu, Satoshi; Akira, Shizuo; Murphy, Gillian; Nagase, Hideaki; Miyaura, Chisato

    2015-12-11

    The stromal cells associated with tumors such as melanoma are significant determinants of tumor growth and metastasis. Using membrane-bound prostaglandin E synthase 1 (mPges1(-/-)) mice, we show that prostaglandin E2 (PGE2) production by host tissues is critical for B16 melanoma growth, angiogenesis, and metastasis to both bone and soft tissues. Concomitant studies in vitro showed that PGE2 production by fibroblasts is regulated by direct interaction with B16 cells. Autocrine activity of PGE2 further regulates the production of angiogenic factors by fibroblasts, which are key to the vascularization of both primary and metastatic tumor growth. Similarly, cell-cell interactions between B16 cells and host osteoblasts modulate mPGES-1 activity and PGE2 production by the osteoblasts. PGE2, in turn, acts to stimulate receptor activator of NF-κB ligand expression, leading to osteoclast differentiation and bone erosion. Using eicosanoid receptor antagonists, we show that PGE2 acts on osteoblasts and fibroblasts in the tumor microenvironment through the EP4 receptor. Metastatic tumor growth and vascularization in soft tissues was abrogated by an EP4 receptor antagonist. EP4-null Ptger4(-/-) mice do not support B16 melanoma growth. In vitro, an EP4 receptor antagonist modulated PGE2 effects on fibroblast production of angiogenic factors. Our data show that B16 melanoma cells directly influence host stromal cells to generate PGE2 signals governing neoangiogenesis and metastatic growth in bone via osteoclast erosive activity as well as angiogenesis in soft tissue tumors. PMID:26475855

  7. Anti-cancer effects of enteric-coated polymers containing mistletoe lectin in murine melanoma cells in vitro and in vivo.

    Science.gov (United States)

    Han, Seung-Yeon; Hong, Chang-Eui; Kim, Hwan-Gyu; Lyu, Su-Yun

    2015-10-01

    In this study, we evaluated the effects of Korean mistletoe (Viscum album L. var. coloratum) coated with a biodegradable polymer (Eudragit(®)) wall on the growth of mouse melanoma in vivo. Oral administration of 4% (430 mg/kg/day) enteric-coated mistletoe resulted in a significant reduction in tumor volume on day 14 compared to the negative control group in B16F10 melanoma-inoculated BDF1 mice. When we measured the survival rate, enteric-coated mistletoe-received mice had a higher survival rate after day 12. Also, we investigated the mechanism involving the cancer cell growth inhibition when melanoma cells were treated with Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) and its extract in vitro. As a result, a significant G0/G1 arrest was observed in both B16BL6 and B16F10 melanoma cells with VCA or mistletoe extract. In addition, VCA or mistletoe extract induced an increase in both early and late apoptosis in cells. When we studied the molecular mechanism, our results showed that VCA and mistletoe extract can increase activated multiple caspases (caspase-1, 3, 4, 5, 6, 7, 8, and 9), dose-dependently. We also found out that VCA and mistletoe treatment causes a significant decrease in the expression of procaspase-3 and 8. PMID:26152904

  8. Local immunosuppressive microenvironment enhances migration of melanoma cells to lungs in DJ-1 knockout mice.

    Directory of Open Access Journals (Sweden)

    Chia-Hung Chien

    Full Text Available DJ-1 is an oncoprotein that promotes survival of cancer cells through anti-apoptosis. However, DJ-1 also plays a role in regulating IL-1β expression, and whether inflammatory microenvironment built by dysregulated DJ-1 affects cancer progression is still unclear. This study thus aimed to compare the metastatic abilities of melanoma cells in wild-type (WT and DJ-1 knockout (KO mice, and to check whether inflammatory microenvironment built in DJ-1 KO mice plays a role in migration of cancer cells to lungs. First, B16F10 melanoma cells (at 6 × 10(4 were injected into the femoral vein of mice, and formation of lung nodules, levels of lung IL-1β and serum cytokines, and accumulation of myeloid-derived suppressor cells (MDSCs were compared between WT and DJ-1 KO mice. Second, the cancer-bearing mice were treated with an interleukin-1 beta (IL-1β neutralizing antibody to see whether IL-1β is involved in the cancer migration. Finally, cultured RAW 264.7 macrophage and B16F10 melanoma cells were respectively treated with DJ-1 shRNA and recombinant IL-1β to explore underlying molecular mechanisms. Our results showed that IL-1β enhanced survival and colony formation of cultured melanoma cells, and that IL-1β levels were elevated both in DJ-1 KO mice and in cultured macrophage cells with DJ-1 knockdown. The elevated IL-1β correlated with higher accumulation of immunosuppressive MDSCs and formation of melanoma module in the lung of DJ-1 KO mice, and both can be decreased by treating mice with IL-1β neutralizing antibodies. Taken together, these results indicate that immunosuppressive tissue microenvironment built in DJ-1 KO mice can enhance lung migration of cancer, and IL-1β plays an important role in promoting the cancer migration.

  9. Detachment of glycolytic enzymes from cytoskeleton of melanoma cells induced by calmodulin antagonists.

    Science.gov (United States)

    Glass-Marmor, L; Beitner, R

    1997-06-11

    Glycolysis, which is the primary energy source in cancer cells, is known to be controlled by allosteric regulators, as well as by reversible binding of glycolytic enzymes to cytoskeleton. We have previously found that different calmodulin antagonists decrease the levels of allosteric activators of glycolysis, and reduce ATP content and cell viability in B16 melanoma cells. Here we report of a novel, additional, mechanism of action of calmodulin antagonists in melanoma cells. We show that these drugs cause a detachment of the glycolytic enzymes, phosphofructokinase (ATP: D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) and aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13), from cytoskeleton of B16 melanoma cells. This effect was dose- and time-dependent, and preceded the decrease in cell viability. The detachment of glycolytic enzymes from cytoskeleton would reduce the provision of local ATP, in the vicinity of the cytoskeleton-membrane and would affect cytoskeleton structure. Since the cytoskeleton is being recognized as an important modulator of cell function, proliferation, differentiation and neoplasia, detachment of the glycolytic enzymes from cytoskeleton induced by calmodulin antagonists, as well as their reported inhibitory action on cell proliferation, make these drugs most promising agents in treatment of cancer. PMID:9218707

  10. Cytotoxicity evaluation of carbon-encapsulated iron nanoparticles in melanoma cells and dermal fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Grudzinski, Ireneusz P., E-mail: ireneusz.grudzinski@wum.edu.pl [Medical University of Warsaw, Department of Toxicology, Faculty of Pharmacy (Poland); Bystrzejewski, Michal [Warsaw University, Department of Physical Chemistry, Faculty of Chemistry (Poland); Cywinska, Monika A.; Kosmider, Anita [Medical University of Warsaw, Department of Toxicology, Faculty of Pharmacy (Poland); Poplawska, Magdalena [Warsaw University of Technology, Department of Organic Chemistry, Faculty of Chemistry (Poland); Cieszanowski, Andrzej [Medical University of Warsaw, Department of Clinical Radiology, Faculty of Medicine (Poland); Ostrowska, Agnieszka [Analytic Centre, University of Life Sciences SGGW (Poland)

    2013-08-15

    Carbon-encapsulated iron nanoparticles (CEINs) are emerging as promising biomedical tools due to their unique physicochemical properties. In this study, the cytotoxic effect of CEINs (the mean diameter distribution ranges 46-56 nm) has been explored by MTT, LDH leakage, Calcein-AM/propidium iodide (PI) and Annexin V-FITC/PI assays in human melanoma (HTB-140), mouse melanoma (B16-F10) cells, and human dermal fibroblasts (HDFs). The results demonstrated that CEINs produce mitochondrial and cell membrane cytotoxicities in a dose (0.0001-100 {mu}g/ml)-dependent manner. Moreover, the studies elucidated some differences in cytotoxic effects between CEINs used as raw and purified materials composing of the carbon surface with acidic groups. Experiments showed that HTB-140 cells are more sensitive to prone early apoptotic events due to raw CEINs as compared to B16-F10 or HDF cells, respectively. Taken together, these results suggest that the amount of CEINs administered to cells and the composition of CEINs containing different amounts of iron as well as the carbon surface modification type is critical determinant of cytotoxic responses in both normal and cancer (melanoma) cells.

  11. Antimetastatic Potentials of Dioscorea nipponica on Melanoma In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Mao-Lin Ho

    2011-01-01

    Full Text Available Recent studies have revealed pleiotropic anticancer and antiproliferative capabilities of Dioscorea nipponica Makino whereas the effect of this plant on metastasis of cancer cells has not been clearly clarified. In the present study, we extracted Dioscorea nipponica Makino with methanol (DNE1, chloroform (DNE2, ethyl acetate (DNE3, n-butanol (DNE4, and water (DNE5. We first demonstrate that DNE3 was found to be effective in reducing the lung metastases formation by about 99.5% as compared to vehicle-treated control animals. When a nontoxic concentration of the extract was treated directly to highly metastatic murin melanoma cells (B16F10 and human melanoma cells (A2058 in vitro, it exerted a dose-dependent inhibitory effect on the invasion (P<.001, motility (P<.001, secretion of MMPs (P<.001, and u-PA (P<.001 of both cell lines. To investigate the possible mechanisms involved in these events, we performed western blot analysis to find that DNE inhibited phosphorylation of Akt. A treatment with DNE3 to B16F10 cells also inhibited the activation of NF-κB and increased the expression of IkappaB. Taken together, these findings suggested that DNE3 could reduce the metastasis of melanoma cells, thereby constituting an adjuvant treatment for metastasis control.

  12. Cytotoxicity evaluation of carbon-encapsulated iron nanoparticles in melanoma cells and dermal fibroblasts

    International Nuclear Information System (INIS)

    Carbon-encapsulated iron nanoparticles (CEINs) are emerging as promising biomedical tools due to their unique physicochemical properties. In this study, the cytotoxic effect of CEINs (the mean diameter distribution ranges 46–56 nm) has been explored by MTT, LDH leakage, Calcein-AM/propidium iodide (PI) and Annexin V-FITC/PI assays in human melanoma (HTB-140), mouse melanoma (B16-F10) cells, and human dermal fibroblasts (HDFs). The results demonstrated that CEINs produce mitochondrial and cell membrane cytotoxicities in a dose (0.0001–100 μg/ml)-dependent manner. Moreover, the studies elucidated some differences in cytotoxic effects between CEINs used as raw and purified materials composing of the carbon surface with acidic groups. Experiments showed that HTB-140 cells are more sensitive to prone early apoptotic events due to raw CEINs as compared to B16-F10 or HDF cells, respectively. Taken together, these results suggest that the amount of CEINs administered to cells and the composition of CEINs containing different amounts of iron as well as the carbon surface modification type is critical determinant of cytotoxic responses in both normal and cancer (melanoma) cells

  13. MALIGNANT MELANOMA – CUTANEOUS METASTASES

    Science.gov (United States)

    Padmavathy, L; Lakshmana Rao, L; Ethirajan, N; Krishna Swamy, B

    2008-01-01

    Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra.1 Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported. PMID:19882041

  14. Multidrug resistance in ocular melanoma.

    OpenAIRE

    McNamara, M.; Clynes, M.; Dunne, B; NicAmhlaoibh, R; Lee, W. R.; Barnes, C; Kennedy, S M

    1996-01-01

    AIMS/BACKGROUND: Metastatic disease in patients with ocular melanoma is resistant to chemotherapy. One of the main mechanisms of modulating multidrug resistance is the expression of the multidrug resistance gene 1 (MDR1) product (p-glycoprotein) by tumour cells. The purpose of this study was to evaluate the frequency of expression of the MDR1 gene in ocular melanoma whose primary treatment was surgical excision or enucleation. METHODS: Twelve recent ocular melanomas were received fresh, snap ...

  15. Camphene isolated from essential oil of Piper cernuum (Piperaceae) induces intrinsic apoptosis in melanoma cells and displays antitumor activity in vivo.

    Science.gov (United States)

    Girola, Natalia; Figueiredo, Carlos R; Farias, Camyla F; Azevedo, Ricardo A; Ferreira, Adilson K; Teixeira, Sarah F; Capello, Tabata M; Martins, Euder G A; Matsuo, Alisson L; Travassos, Luiz R; Lago, João H G

    2015-11-27

    Natural monoterpenes were isolated from the essential oil of Piper cernuum Vell. (Piperaceae) leaves. The crude oil and the individual monoterpenes were tested for cytotoxicity in human tumor cell lineages and B16F10-Nex2 murine melanoma cells. In the present work we demonstrate the activity of camphene against different cancer cells, with its mechanism of action being investigated in vitro and in vivo in murine melanoma. Camphene induced apoptosis by the intrinsic pathway in melanoma cells mainly by causing endoplasmic reticulum (ER) stress, with release of Ca(2+) together with HmgB1 and calreticulin, loss of mitochondrial membrane potential and up regulation of caspase-3 activity. Importantly, camphene exerted antitumor activity in vivo by inhibiting subcutaneous tumor growth of highly aggressive melanoma cells in a syngeneic model, suggesting a promising role of this compound in cancer therapy. PMID:26471302

  16. Isolation and Identification of Cancer Stem-Like Cells from Murine Melanoma Cell Lines

    Institute of Scientific and Technical Information of China (English)

    Jun Dou; Kai Hu; Ning Gu; Meng Pan; Ping Wen; Yating Li; Quan Tang; Lili Chu; Fengshu Zhao; Chuilian Jiang; Weihua Hu

    2007-01-01

    In current study, cancer stem-like cells in the murine melanoma B16F10 cells were investigated. CD phenotypes of the B16F10 cells were analyzed by flow cytometry, and the specific CD phenotype cells from the B16F10 cells were isolated by MACS. Then we used colony formation assay in soft agar media, the cell growth assay in serum-free culture media as well as the tumorigenicity investigation of the specific CD phenotype cells in C57BL/6 mice,respectively, to identify cancer stem-like cells in the B16F10 cells. The results showed that the B16F10 cells could form spherical clones in serum-free culture media, and the rate of clonegenesis of CD133+, CD44+ and CD44+CD133+ cells was higher than that of CD133-, CD44- and CD44+CD133- cells in soft agar media, respectively.The tumorigenic potential of CD133+, CD44+, CD44+CD133+ cells and CD44+CD133+CD24+ cells was stronger than that of CD133-, CD44-, CD44+CD133- cells and CD44+CD133+CD24- cells in mice, respectively. In conclusion, the CD44+CD133+CD24+ cells have some biological properties of cancer stem-like cells or are highly similar to the characteristics of cancer stem cells (CSC). These results provide an important method for identifying cancer stem-like cells in B16F10 cells and for further cancer target therapy.

  17. Nodular amelanotic melanoma

    Directory of Open Access Journals (Sweden)

    Nalamwar Rashmi

    2010-01-01

    Full Text Available We report a case of 65-year-old male patient who presented with multiple erythematous papules coalescing to form a nodular mass over posterior aspect of right thigh of six months duration. His general and systemic examinations were within normal range except for right inguinal lymphadenopathy. Biopsy from the lesion was done, which showed diffuse infiltrate of nests of atypical melanocytes extending upto reticular dermis. Malignant cells were positive for S100 and human melanin black 45(HMB 45. Hence, a diagnosis of amelanotic melanoma (AM - Clarke level IV and TNM stage III was reached. MRI of involved leg showed fungating soft tissue mass in the posterolateral aspect of right thigh and metastatic right inguinal adenopathy. Fine needle aspiration cytology (FNAC from the right inguinal nodes confirmed metastasis of melanoma. The patient was referred to oncosurgery department for further management.

  18. Life After Transplant

    Science.gov (United States)

    ... to 20-year friendship Supporter stories Valerie Sun - bone marrow transplant patient advocate Jeff and Kim take their life- ... transplant and other treatment options What is a bone marrow transplant How a bone marrow transplant works Transplant process ...

  19. Treatment Before Transplant

    Science.gov (United States)

    ... to 20-year friendship Supporter stories Valerie Sun - bone marrow transplant patient advocate Jeff and Kim take their life- ... transplant and other treatment options What is a bone marrow transplant How a bone marrow transplant works Transplant process ...

  20. Drivers of melanoma susceptibility

    OpenAIRE

    Robles Espinoza, Carla Daniela

    2015-01-01

    Cutaneous melanoma is a cancer of melanocytes, the pigment-producing cells in our skin. It is one of the most aggressive human malignancies, constituting only about 2% of all dermatological cancers but being responsible for over 75% of all deaths from skin cancer. It has recently become a major public health problem, as it is now the fifth most common cancer in the United Kingdom after its incidence more than quadrupled in the last three decades. For these reasons, understanding the biologica...

  1. Vitamins and Melanoma

    OpenAIRE

    Irene Russo; Francesca Caroppo; Mauro Alaibac

    2015-01-01

    A tremendous amount of information was published over the past decades in relation to the role of vitamins in various neoplastic diseases. In particular, several studies showed an inverse relationship between selected vitamins intake and cancer risk. In this review we will focus on the role played by vitamins in melanoma with particular regard to vitamin A, D, K, E and C. Given that vitamin supplementation is easy, convenient, and readily accepted by patients, in the future the use of vitamin...

  2. Malignant melanoma of choroid

    Directory of Open Access Journals (Sweden)

    Manohar S

    1991-01-01

    Full Text Available Four cases of malignant melanoma of the choroid are reported due to rarity of the condition in India. One of the cases presented with Naevus of Ota. All the cases had typical clinical and investigative features. All cases were enucleated. Histopathologically three of them were of mixed type and one was of the epithelioid type. Two of the cases were seen in patients below 40 years of age.

  3. Chemoprevention of Melanoma

    OpenAIRE

    Madhunapantula, SubbaRao V.; Robertson, Gavin P.

    2012-01-01

    Despite advances in drug discovery programs and molecular approaches for identifying the drug targets, incidence and mortality rates due to melanoma continues to rise at an alarming rate. Existing preventive strategies generally involve mole screening followed by surgical removal of the benign nevi and abnormal moles. However, due to lack of effective programs for screening and disease recurrence after surgical resection there is a need for better chemopreventive agents. Although sunscreens h...

  4. Principles of Melanoma Staging.

    Science.gov (United States)

    Boland, Genevieve M; Gershenwald, Jeffrey E

    2016-01-01

    Although now commonplace in contemporary cancer care, the systematic approach to classification of disease-specific cancers into a formalized staging system is a relatively modern concept. Overall, the goals of cancer staging are to characterize the status of cancer at a specific moment in time, risk stratify, facilitate prognostication, and inform clinical decision making. The revisions to the American Joint Committee on Cancer (AJCC) melanoma staging system over time reflect changes in our understanding of the biology of the disease. Since the 1st edition, where tumor thickness was defined anatomically by its relationship to the reticular or papillary dermis (Clark level) as well as tumor thickness (Breslow thickness), there have been significant strides in our use of clinicopathological variables to stratify low- versus high-risk patients. Management of the regional nodal basin has also changed dramatically over time, impacted by techniques such as lymphatic mapping and sentinel lymph node biopsy (SLNB) and changes in pathological evaluation of the regional lymph nodes. Additionally, stratification of distant metastases has evolved as survival outcomes have been shown to vary based upon anatomic site of metastases and serum lactate dehydrogenase levels. The variables in use in the current (7th edition) AJCC staging system are surrogate markers of biology with validated impact of survival outcomes. Going forward, it is likely that these and additional clinicopathological factors will be integrated with molecular and other correlates of melanoma tumor biology to further refine and personalize melanoma staging. PMID:26601861

  5. Surgery of Primary Melanomas

    International Nuclear Information System (INIS)

    Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas

  6. Surgery of Primary Melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Rutkowski, Piotr, E-mail: rutkowskip@coi.waw.pl; Zdzienicki, Marcin; Nowecki, Zbigniew I. [Soft Tissue/Bone Sarcoma and Melanoma Department, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Akkooi, Alexander C. J. van [Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

    2010-05-11

    Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas.

  7. em cultura de células de melanoma

    Directory of Open Access Journals (Sweden)

    Fernanda Vieira Berti

    2007-01-01

    Full Text Available Identification, extraction, isolation and characterization of plant derived active molecules that modulate cell viability are of great clinical and pharmacological interest. Phytochemical tests have been used to demonstrate the presence of several compounds both from the primary and secondary metabolism of Aloe vera L. Aloin, an anthraquinone isolated from the chlorophyll parenchyma of A. vera L, is known for its biological activity. The antitumoral activity of aloin and the chlorophyll parenchyma extract was evaluated in vitro with the use of murine melanoma cell line B16F10. Cells incubated with 5% CO 2 at 37ºC were treated with different aloin and parenchyma extract concentrations. Both affected cellular stability, acting as modulators of tumoral cell viability. Experimental data were fitted to a developed mathematical model. From the fitting parameters we concluded that the chlorophyll parenchyma extract is 2.3 times more toxic to the cell than aloin.

  8. Effects of taurolidine on radiosensitivity of murine melanoma cells and its mechanism

    International Nuclear Information System (INIS)

    Objective: To observe the effects of taurolidine on radiosensitivity of B16-F10 cells of murine melanoma via the enhancement of Bax and Bad proteins and induction of Bcl-2 protein. Methods: The apoptosis of B16-F10 cells was assessed after treated with 0, 10, 25, 50, 100 and 150 μmol·L-1 taurolidine, clone survival assay was used to detect the radiosensitivity of B16-F10 cells, and protein expressions were determined by Western blotting. Results: The apoptosis of 5% cells was induced in a dose-and time-dependent manner after B16-F10 cells were treated with 50 μmol·L-1 taurolidine. The survival rate decreased after treated with tautolidine in combination with 2 Gy X-irradiation with the increase of taurolidine concentration and doses of irradiation (P0 and SER Dq) also increased with the increase of its concentration, there was significant difference between 50 μmol·L-1 taurolidine group and 10 μmol·L-1 taurolidine group (P<0.05); meantime, the level of proapototic protein Bax and Bad increased and the level of antiapoptotic protein Bcl-2 reduced. Conclusion: Taurolidine in combination with irradiation can enhance the radiosensitivity by the mediation of Bcl-2 family protein. (authors)

  9. Irradiation of choroidal melanoma with iodine 125 ophthalmic plaque

    International Nuclear Information System (INIS)

    Radioactive iodine 125 is a low-energy γ isotope with physical characteristics suitable for irradiation of intraocular tumors. Metal ophthalmic applicators have been designed to shield vital ocular structures while allowing irradiation of the tumor. We compared the radiation effects of iodine 125 and cobalt 60. The Greene melanoma was transplanted into the suprachoroidal space of rabbits. The tumor then grew as an intraocular mass, was irradiated, and was followed up for two months before enucleation. Histopathologic examiation defined the extent of the radiation damage to the tumor and other ocular structures from the iodine 125 and from the cobalt 60. The eye irradiated with iodine 125 suffered minimal radiation damage, whereas the tumor was sterilized. The eye irradiated with cobalt 60 showed substantial radiation damage, and the melanoma was incompletely treated. Our results support the use of iodine 125 in treating intraocular tumors. More research is needed as to optimum total dose and dose rate

  10. Construction of Egr-IFN γ and it's expression in B16 cells induced by ionizing irradiation

    International Nuclear Information System (INIS)

    Mouse IFN γ cDNA was ligated to downstream of Egr-1 promoter to construct Egr-IFN γ plasmid. The recombined plasmids were transfected into B16 cells with liposome, then the expression of IFN γ after different doses of X-ray irradiation and the time course of expression were detected by ELISA. The results showed that the expression levels in experimental groups were higher than that in the control group obviously (p<0.01); 6h after 2 Gy X-ray irradiation, the expression of IFN γ was highest (p<0.01); The B16 cells transfected were given 2 Gy X-ray irradiation every 24h, the expression level was highest after first irradiation (p<0.01) and then decrease gradually. The results indicated that ionizing irradiation can activate the Egr-IFN γ recombined plasmid and regulate the expression of IFN γ gene in B16 cells. The observation may be of potential significance in tumor therapy

  11. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    International Nuclear Information System (INIS)

    Research highlights: → Strong ADAM15 expression is found in normal melanocytes. → ADAM15 expression is significantly downregulated in patients with melanoma metastasis. → TGF-β can downregulate ADAM15 expression in melanoma cells. → Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. → Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-γ and TGF-β downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  12. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ungerer, Christopher; Doberstein, Kai [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning [Department of Dermatology, Clinic of the Goethe-University, Theodor-Stern-Kai, Frankfurt (Germany); Boehm, Beate [Division of Rheumatology, Goethe University, Frankfurt am Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Dummer, Reinhard [Department of Pathology, Institute of Surgical Pathology, University Hospital, Zurich (Switzerland); Mihic-Probst, Daniela [Department of Dermatology, University Hospital Zurich (Switzerland); Gutwein, Paul, E-mail: p.gutwein@med.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany)

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  13. Liver transplantation

    OpenAIRE

    Rodríguez-Perálvarez, M; De La Mata, M; Burroughs, A K

    2014-01-01

    Purpose of review: Long-term survival of liver transplant recipients is threatened by increased rates of de-novo malignancy and recurrence of hepatocellular carcinoma (HCC), both events tightly related to immunosuppression. Recent findings: There is accumulating evidence linking increased exposure to immunosuppressants and carcinogenesis, particularly concerning calcineurin inhibitors (CNIs), azathioprine and antilymphocyte agents. A recent study including 219 HCC transplanted patients sh...

  14. IL-24/MDA-7 Suppressed the Transplantation Tumor in BALB/c Mice

    Institute of Scientific and Technical Information of China (English)

    Jiancheng Xue; Changlin Wu; Yi Zhu; Lan Li; Xintang Dang; Shaoguang Qu; Fang Liu

    2006-01-01

    It is well-documented that interleukin-24 (IL-24) can induce apoptosis in a large spectrum of human cancer derived cell lines, but the effect of MDA-7/IL-24 gene transfer on mouse melanoma cells remains unknown. The eukaryotic expressing plasmid of IL-24 (pEGFP-IL-24) was constructed by DNA recombination technique. The recombination plasmid and empty vector were transfected into B16F0 cells and the expressions of IL-24 were determined by LSM, the proliferation of B16F0 cells was measured by MTT assay, and apoptosis rate and cell-cycle distribution of B16F0 cells were measured by FCM. The inhibitory effect of IL-24 gene transfection in mouse solid tumor was observed and measured. Compared with the control, the proliferation of B16F0 cells was inhibited by transfection with pEGFP-IL-24 and the G2/M phase of the transfected cells was also increased.Moreover, the percentage of mice with detectable tumor was decreased after inoculated with B16F0 cells transfected with pEGFP-IL-24. Growth rate of tumor in mouse model was significantly inhibited in IL-24 gene therapy group compared with the control. Proliferation of B16F0 cells was inhibited by pEGFP-IL-24 transfection.The intratumor injection of pEGFP-IL-24 could inhibit the growth of solid tumor in mice remarkably.

  15. Design and Evaluation of New Tc-99m-Labeled Lactam Bridge-Cyclized Alpha-MSH Peptides for Melanoma Imaging

    OpenAIRE

    Guo, Haixun; Gallazzi, Fabio; Miao, Yubin

    2013-01-01

    The purpose of this study was to examine the melanoma targeting and imaging properties of new 99mTc-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (α-MSH) peptides using bifunctional chelating agents. MAG3-GGNle-CycMSHhex, AcCG3-GGNle-CycMSHhex and HYNIC-GGNle-CycMSHhex peptides were synthesized and their melanocortin-1 (MC1) receptor binding affinities were determined in B16/F1 melanoma cells. The biodistribution of 99mTc-MAG3-GGNle-CycMSHhex, 99mTc-AcCG3-GGNle-CycMSHhex...

  16. Transplant psychiatry.

    Science.gov (United States)

    Potts, S G

    2009-12-01

    Transplant units increasingly recognise a need for assistance from psychiatrists and psychologists in the assessment and management of potential transplant recipients and live donors. This arises from the various known associations between mental disorder and the need for transplantation; the intensifying requirement to select carefully among the potential recipients and donors of scarce human organs; and the drive to maximise transplant outcomes by optimising all aspects of treatment after surgery. There is good evidence that careful, protocol-guided selection among potential candidates for transplantation with alcoholic liver disease helps ensure outcomes at least as good as for other forms of liver disease. The evidence base in other areas is less robust, but the principles guiding the psychiatric assessment are broadly the same. There is an increasing need for psychiatric assessment of potential live organ donors, in order to minimise the risks they run, and in the case of altruistic donation this is now mandatory in UK law. PMID:21152475

  17. Keeping a watch on melanoma.

    Science.gov (United States)

    Casparian, J Michael; Rodewald, Erin J

    2002-05-01

    When performing a total body skin examination, we discovered a melanoma in situ when a patient took off her wristwatch. This case illustrates the importance of removing jewelry when performing a complete skin examination. Furthermore, the location of this lesion highlights the association between malignant melanoma and intermittent sun exposure. PMID:12041820

  18. Snake venoms components with antitumor activity in murine melanoma cells

    International Nuclear Information System (INIS)

    Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)

  19. 203Pb-Labeled Alpha-Melanocyte-Stimulating Hormone Peptide as an Imaging Probe for Melanoma Detection

    Energy Technology Data Exchange (ETDEWEB)

    Yubin, Miao; Figueroa, Said D.; Fisher, Darrell R.; Moore, Herbert A.; Testa, Richard F.; Hoffman, Timothy J.; Quinn, Thomas P.

    2008-05-01

    Abbreviations: a-MSH; alpha melanocyte stimulating hormone, DOTA; 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, Re(Arg11)CCMSH; DOTA-[Cys3,4,10, D-Phe7, Arg11]a-MSH3-13, NDP; [Nle4,d-Phe7] a-MSH3-13. Abstract Peptide-targeted alpha therapy with 200 mCi of 212Pb-DOTA-Re(Arg11)CCMSH cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-day study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patient specific dosimetry and to monitor the tumor response to 212Pb-DOTA-Re(Arg11)CCMSH therapy. The purpose of this study was to evaluate the potential of 203Pb-DOTA-Re(Arg11)CCMSH as a matched-pair SPECT imaging agent for 212Pb-DOTA-Re(Arg11)CCMSH. Method: DOTA-Re(Arg11)CCMSH was labeled with 203Pb in 0.5 M NH4OAc buffer at pH 5.4. The internalization and efflux of 203Pb-DOTA-Re(Arg11)CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of 203Pb-DOTA-Re(Arg11)CCMSH were examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT imaging study was performed with 203Pb-DOTA-Re(Arg11)CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h post-injection. Results: 203Pb-DOTA-Re(Arg11)CCMSH was easily prepared in NH4OAc buffer and completely separated from the excess non-radiolabeled peptide by RP-HPLC. 203Pb-DOTA-Re(Arg11)CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of 203Pb-DOTA-Re(Arg11)CCMSH activity internalized after a 20-min incubation at 25C. After incubating the cells in culture media for 20 min, 78% of internalized activity remained in the cells. 203Pb-DOTA-Re(Arg11)CCMSH exhibited similar biodistribution pattern with 212Pb-DOTA-Re(Arg11)CCMSH in B16/F1 melanoma-bearing mice. 203Pb-DOTA-Re(Arg11)CCMSH exhibited the peak tumor uptake of 12.00 +/- 3.20 %ID/g at 1 h post-injection. The tumor uptake gradually decreased to 3.43 +/- 1.12 %ID/g at 48 h post-injection. 203Pb-DOTA-Re(Arg11)CCMSH exhibited the peak tumor to kidney

  20. Primary Desmoplastic Melanoma of the Penis

    OpenAIRE

    Chu, Julia T.; Liss, Michael A; Wu, William W.; Atreya Dash; Di Lu

    2015-01-01

    Desmoplastic melanomas are rare amelanotic melanomas that usually occur on skin with sun exposure. In this report, we present a 72-year-old man who presented with a desmoplastic melanoma of the penis. To our knowledge this represents the first reported case of primary desmoplastic melanoma of the penis. We discuss the pathologic differential and histologic evaluation.

  1. Brain metastases from malignant melanoma.

    Science.gov (United States)

    Chiarion-Sileni, Vanna; Murr, Rita; Pigozzo, Jacopo; Sarti, Samanta; Tomassi, Ottaviano; Romanini, Antonella

    2003-01-01

    Metastatic spread of tumour cells detached from melanoma into the central nervous system (CNS) occurs haematogenously since lymphatic drainage is absent in the brain. CNS metastases occur in 10 to 40% of melanoma patients in clinical studies and up to 90% in autopsy studies. Headache is the most common presenting symptom, but brain metastases should be suspected in all melanoma patients with new neurologic findings. Magnetic resonance imaging is the best diagnostic technique for detecting CNS metastases. Median survival of melanoma patients with CNS metastases ranges between 2 and 8 months. The optimal treatment of melanoma patients with CNS metastases depends on the objective situation, often surgery, radiosurgery, whole brain radiotherapy and chemotherapy are used in combination to obtain longer remissions and optimal symptom relieve. PMID:14732883

  2. Ca2+-induced changes in energy metabolism and viability of melanoma cells

    OpenAIRE

    Glass-Marmor, L; Penso, J; Beitner, R

    1999-01-01

    Cancer cells are characterized by a high rate of glycolysis, which is their primary energy source. We show here that a rise in intracellular-free calcium ion (Ca2+), induced by Ca2+-ionophore A23187, exerted a deleterious effect on glycolysis and viability of B16 melanoma cells. Ca2+-ionophore caused a dose-dependent detachment of phosphofructokinase (EC 2.7.1.11), one of the key enzymes of glycolysis, from cytoskeleton. It also induced a decrease in the levels of glucose 1,6-bisphosphate and...

  3. Human hemokinin-1 promotes migration of melanoma cells and increases MMP-2 and MT1-MMP expression by activating tumor cell NK1 receptors.

    Science.gov (United States)

    Zhang, Yixin; Li, Xiaofang; Li, Jingyi; Hu, Hui; Miao, Xiaokang; Song, Xiaoyun; Yang, Wenle; Zeng, Qian; Mou, Lingyun; Wang, Rui

    2016-09-01

    Receptors and their regulatory peptides are aberrantly expressed in tumors, suggesting a potential tumor therapy target. Human hemokinin-1 (hHK-1) is a tachykinin peptide ligand of the neurokinin-1 (NK1) receptor which is overexpressed in melanoma and other tumor tissues. Here, we investigated the role of hHK-1 and the NK1 receptor in melanoma cell migration. NK1 receptor expression was associated with melanoma metastatic potential. Treatment with hHK-1 significantly enhanced A375 and B16F10 melanoma cell migration and an NK1 receptor antagonist L732138 blocked this effect. MMP-2 and MT1-MMP expression were up-regulated in hHK-1-treated melanoma cells and cell signaling data suggested that hHK-1 induced phosphorylation of ERK1/2, JNK and p38 by way of PKC or PKA. Kinase activation led to increased MMP-2 and MT1-MMP expression and melanoma cell migration induced by hHK-1. Thus, hHK-1 and the NK1 receptor are critical to melanoma cell migration and each may be a promising chemotherapeutic target. PMID:27458061

  4. Evaluation of epidermal growth factor interaction with cell surface and its accumulation in nuclei of lung carcinoma, epidermoid carcinoma and melanoma cell lines

    International Nuclear Information System (INIS)

    Specificity of binding to cell surface and nuclear accumulation of labelled epidermal growth factor (EGF) was investigated in lung carcinoma (A549), epidermoid carcinoma (HEp-2) and melanoma (B16) cell lines. It was demonstrated that the labelled EGF was bound specifically to the cell surface in line A549, HEp-2 and B16 cells; the latter exhibiting the lowest binding capacity and highest binding affinity. Comparison of nuclear accumulation of the labelled growth factor in these cell lines indicated, that melanoma cell line specifically accumulated the 125I-EGF in nuclei whereas A549 and HEp-2 did not. Thus, in order to evaluate the effect of EGF in various cells, a strict control of binding affinity and background binding is required. (author). 19 refs, 3 figs, 1 tab

  5. Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo

    DEFF Research Database (Denmark)

    Ale, Marcel Tutor; Maruyama, Hiroko; Tamauchi, Hidekazu;

    2011-01-01

    performed using cell viability analysis and showed that SIG and MTA fucoidans significantly decreased the viable number of LCC and MC cells in a dose–response fashion. Histochemical staining showed morphological changes of melanoma B16 cells after exposure to fucoidan. The observed changes were indicative......Fucoidan is known to exhibit crucial biological activities, including anti-tumor activity. In this study, we examined the influence of crude fucoidan extracted from Sargassum sp. (MTA) and Fucus vesiculosus (SIG) on Lewis lung carcinoma cells (LCC) and melanoma B16 cells (MC). In vitro studies were...... of crude fucoidan induced apoptosis. Male C57BL/6JJCL mice were subjected to daily i.p. injections over 4 days with either SIG or MTA fucoidan (50 mg/kg body wt.). The cytolytic activity of natural killer (NK) cells was enhanced by crude fucoidan in a dose-dependent manner as indicated by 51Cr...

  6. Melanoma cell expression of CD200 inhibits tumor formation and lung metastasis via inhibition of myeloid cell functions.

    Directory of Open Access Journals (Sweden)

    Fatemeh Talebian

    Full Text Available CD200 is a cell surface glycoprotein that functions through engaging CD200 receptor on cells of the myeloid lineage and inhibits their functions. Expression of CD200 has been implicated in a variety of human cancer cells including melanoma cells and has been thought to play a protumor role. To investigate the role of cancer cell expression of CD200 in tumor formation and metastasis, we generated CD200-positive and CD200-negative B16 melanoma cells. Subcutaneous injection of CD200-positive B16 melanoma cells inhibited tumor formation and growth in C57BL/6 mice but not in Rag1⁻/⁻C57BL/6 mice. However, i.v. injection of CD200-positive B16 melanoma cells dramatically inhibited tumor foci formation in the lungs of both C57BL/6 and Rag1⁻/⁻C57BL6 mice. Flow cytometry analysis revealed higher expression of CD200R in Gr1⁺ myeloid cells in the lung than in peripheral myeloid cells. Depletion of Gr1⁺ cells or stimulation of CD200R with an agonistic antibody in vivo dramatically inhibited tumor foci formation in the lungs. In addition, treatment with tumor antigen specific CD4 or CD8 T cells or their combination yielded a survival advantage for CD200 positive tumor bearing mice over mice bearing CD200-negative tumors. Taken together, we have revealed a novel role for CD200-CD200R interaction in inhibiting tumor formation and metastasis. Targeting CD200R may represent a novel approach for cancer immunotherapy.

  7. Studies of Secondary Melanoma on C57BL/6J Mouse Liver Using 1H NMR Metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Ju; Isern, Nancy G.; Burton, Sarah D.; Hu, Jian Z.

    2013-10-31

    NMR metabolomics, consisting of solid state high resolution (hr) magic angle spinning (MAS) 1H NMR (1H hr-MAS), liquid state high resolution 1H-NMR, and principal components analysis (PCA) has been used to study secondary metastatic B16-F10 melanoma in C57BL/6J mouse liver . The melanoma group can be differentiated from its control group by PCA analysis of the absolute concentrations or by the absolute peak intensities of metabolites from either 1H hr-MAS NMR data on intact liver tissues or liquid state 1H-NMR spectra on liver tissue extracts. In particular, we found that the absolute concentrations of alanine, glutamate, creatine, creatinine, fumarate and cholesterol are elevated in the melanoma group as compared to controls, while the absolute concentrations of succinate, glycine, glucose, and the family of linear lipids including long chain fatty acids, total choline and acylglycerol are decreased. The ratio of glycerophosphocholine to phosphocholine is increased by about 1.5 fold in the melanoma group, while the absolute concentration of total choline is actually lower in melanoma mice. These results suggest the following picture in secondary melanoma metastasis: Linear lipid levels are decreased by beta oxidation in the melanoma group, which contributes to an increase in the synthesis of cholesterol, and also provides an energy source input for TCA cycle. These findings suggest a link between lipid oxidation, the TCA cycle and the hypoxia-inducible factors (HIF) signal pathway in tumor metastases. Thus this study indicates that the metabolic profile derived from NMR analysis can provide a valuable bio-signature of malignancy and cell hypoxia in metastatic melanoma.

  8. A 99mTc(CO)3-labeled pyrazolyl-α-melanocyte-stimulating hormone analog conjugate for melanoma targeting

    International Nuclear Information System (INIS)

    Melanoma primary tumors can be, in most cases, removed surgically, whereas there is no satisfactory treatment for metastatic melanoma, being almost always lethal at this stage. Therefore, early detection of primary melanoma tumors is essential. The finding that melanocortin-1 receptor (MC1R) is overexpressed in isolated melanoma cells and melanoma tissues led to the radiolabeling of several α-melanocyte-stimulating hormone (α-MSH) analogs for early detection and treatment of melanoma. We have coupled the α-MSH analog Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2, through the ε-amino group of Lys11, to a pyrazolyl-containing chelator (pz). The resulting pz-α-MSH analog reacted with the fac-[99mTc(CO)3]+ moiety, giving [Ac-Nle4,Asp5,D-Phe7,Lys11(pz-99mTc(CO)3)]α-MSH4-11 in high yield, high specific activity and high radiochemical purity. This radioconjugate, which presents remarkable stability in vitro, exhibited time- and temperature-dependent internalization (4 h at 37oC; 56.7% maximum internalization) and high cellular retention (only 38% was released from the cell after 5 h) in murine melanoma B16F1 cells. A significant tumor uptake [4.2±0.9%ID/g, at 4 h postinjection (p.i.)] was also obtained in melanoma-bearing C57BL6 mice. The in vivo affinity and specificity of the radioconjugate to MC1R were demonstrated by receptor-blocking studies with the potent NDP-MSH agonist (63.5% reduction in tumor uptake at 4 h p.i.)

  9. Oral amelanotic melanoma of the maxilla.

    Directory of Open Access Journals (Sweden)

    Nasrollah Saghravanian

    2014-12-01

    Full Text Available Amelanotic melanoma is a variant of malignant melanoma comprising 2% to 8% of all malignant melanomas. The amelanotic presentation of melanoma in the oral cavity is extremely rare and has been reported only occasionally in the literature. Moreover, the lack of melanin makes these tumors difficult to diagnose than that of pigmented lesions and the prognosis tends to be poorer. Herein, we report an amelanotic melanoma involving the oral mucosa of the maxilla in a 27 year-old male.

  10. Preventing Melanoma PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2015-06-02

    This 60 second public service announcement is based on the June 2015 CDC Vital Signs report. Skin cancer is the most common form of cancer in the U.S. In 2011, there were more than 65,000 cases of melanoma, the most deadly form of skin cancer. Learn how everyone can help prevent skin cancer.  Created: 6/2/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 6/2/2015.

  11. [Heart transplantation].

    Science.gov (United States)

    Fukushima, Norihide; Matsuda, Hikaru

    2005-11-01

    While nearly 4,000 patients undergo heart transplantation (HTx) every year in the world, only 27 HTx were performed since February, 1999, because of very strict Organ Transplantation Law in Japan. All were treated with triple immunosuppressive regimen. Although two patients died of infection 4 months and 4 years after HTx, respectively, 23 were discharged and 16 returned to work or go to school. New immunosuppressive drugs, such as sirolimus and everolimus, treatment of presensitized patients before transplantation using cyclophosphamide and intravenous globulin infusion, compact implantable left ventricular assist supports and the future of pediatric HTx in Japan are discussed. PMID:16277260

  12. Facial Transplantation.

    Science.gov (United States)

    Russo, Jack E; Genden, Eric M

    2016-08-01

    Reconstruction of severe facial deformities poses a unique surgical challenge: restoring the aesthetic form and function of the face. Facial transplantation has emerged over the last decade as an option for reconstruction of these defects in carefully selected patients. As the world experience with facial transplantation grows, debate remains regarding whether such a highly technical, resource-intensive procedure is warranted, all to improve quality of life but not necessarily prolong it. This article reviews the current state of facial transplantation with focus on the current controversies and challenges, with particular attention to issues of technique, immunology, and ethics. PMID:27400850

  13. GM3 ganglioside: a novel target for the therapy against melanoma

    International Nuclear Information System (INIS)

    Malignant melanoma is a tumor with a steeply increasing incidence and scarce therapeutic options once metastatic. Currently, no vaccine is widely commercially available for melanoma treatment or prevention. The overexpression of GM3 ganglioside in murine and human melanomas and its important role in tumor progression makes this self antigen a potential target for preventive immunotherapy of this neoplasm. Previously, we have shown that preventive vaccination with GM3/VSSP induced a specific antitumor response; and elicited the rejection of syngeneic GM3-positive melanoma cells in immunized mice. In the present paper, we published the induction of a potent antitumor effect of this vaccine administered in a minimal residual disease B16 melanoma model. These findings propose the GM3/VSSP vaccine as a therapy designed to elicit and/or boost antitumor immunity in patients with minimal residual disease after surgery; thereby preventing or prolonging the time to recurrence. This is an important issue of the clinical setting because patients with stage II melanoma were reported to have 60% chance of survival 5 years after surgery. In addition, we examined the mechanisms by which this immunogen confers tumor protection. Surprisingly, in spite of the glycolipidic nature of this antigen, we have found that induction of anti-GM3 IgG antibodies and tumor- specific IFN γ secreting CD8+ T cells correlated with tumor protection. As a result, these findings demonstrate, for the first time, the direct involvement of the cellular immune response in the anti-tumor protection induced by a ganglioside-based vaccine

  14. Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy.

    Science.gov (United States)

    Viallard, Claire; Chezal, Jean-Michel; Mishellany, Florence; Ranchon-Cole, Isabelle; Pereira, Bruno; Herbette, Aurélie; Besse, Sophie; Boudhraa, Zied; Jacquemot, Nathalie; Cayre, Anne; Miot-Noirault, Elisabeth; Sun, Jian-Sheng; Dutreix, Marie; Degoul, Françoise

    2016-03-15

    Radiolabelled melanin ligands offer an interesting strategy for the treatment of disseminated pigmented melanoma. One of these molecules, ICF01012 labelled with iodine 131, induced a significant slowing of melanoma growth. Here, we have explored the combination of [131I]ICF01012 with coDbait, a DNA repair inhibitor, to overcome melanoma radioresistance and increase targeted radionuclide therapy (TRT) efficacy. In human SK-Mel 3 melanoma xenograft, the addition of coDbait had a synergistic effect on tumor growth and median survival. The anti-tumor effect was additive in murine syngeneic B16Bl6 model whereas coDbait combination with [131I]ICF01012 did not increase TRT side effects in secondary pigmented tissues (e.g. hair follicles, eyes). Our results confirm that DNA lesions induced by TRT were not enhanced with coDbait association but, the presence of micronuclei and cell cycle blockade in tumor shows that coDbait acts by interrupting or delaying DNA repair. In this study, we demonstrate for the first time, the usefulness of DNA repair traps in the context of targeted radionuclide therapy. PMID:26887045

  15. Suppression of tumorigenicity and metastatic potential of melanoma cells by transduction of interferon gene

    Directory of Open Access Journals (Sweden)

    Lykhova A. A.

    2014-01-01

    Full Text Available The aim of this study was to investigate an inhibitory effect of baculovirus-mediated transduction of the murine interferon-beta gene on mouse melanoma in vitro and in vivo. Methods. Studies were performed on B16 mouse melanoma (MM-4 cell line. Transduction, immunocytochemical and tumor cell biology approaches have been used in this study. Results. Transduction of MM-4 cells by the recombinant baculovirus with IFN-beta gene is accompanied by morphological changes of tumor cells, suppression of cell proliferation, significant inhibition of platting efficiency of cells and their colonies formation in semisolid agar. Moreover, transduction of melanoma MM-4 cells by the baculovirus IFN-transgene leads to inhibition of tumorigenicity and metastatic ability of the cells in vivo. The intravenous administration of recombinant baculovirus vector with IFN gene inhibits growth of metastases induced in the lungs of mice by intravenously injected tumor cells. Conclusions. Transduction of mouse melanoma cells by the recombinant baculovirus with murine IFN-beta gene inhibits their proliferative potential, tumorigenicity and metastatic activity.

  16. Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy

    Science.gov (United States)

    Viallard, Claire; Chezal, Jean-Michel; Mishellany, Florence; Ranchon-Cole, Isabelle; Pereira, Bruno; Herbette, Aurélie; Besse, Sophie; Boudhraa, Zied; Jacquemot, Nathalie; Cayre, Anne; Miot-Noirault, Elisabeth; Sun, Jian-Sheng; Dutreix, Marie; Degoul, Françoise

    2016-01-01

    Radiolabelled melanin ligands offer an interesting strategy for the treatment of disseminated pigmented melanoma. One of these molecules, ICF01012 labelled with iodine 131, induced a significant slowing of melanoma growth. Here, we have explored the combination of [131I]ICF01012 with coDbait, a DNA repair inhibitor, to overcome melanoma radioresistance and increase targeted radionuclide therapy (TRT) efficacy. In human SK-Mel 3 melanoma xenograft, the addition of coDbait had a synergistic effect on tumor growth and median survival. The anti-tumor effect was additive in murine syngeneic B16Bl6 model whereas coDbait combination with [131I]ICF01012 did not increase TRT side effects in secondary pigmented tissues (e.g. hair follicles, eyes). Our results confirm that DNA lesions induced by TRT were not enhanced with coDbait association but, the presence of micronuclei and cell cycle blockade in tumor shows that coDbait acts by interrupting or delaying DNA repair. In this study, we demonstrate for the first time, the usefulness of DNA repair traps in the context of targeted radionuclide therapy. PMID:26887045

  17. Hair Dyes Resorcinol and Lawsone Reduce Production of Melanin in Melanoma Cells by Tyrosinase Activity Inhibition and Decreasing Tyrosinase and Microphthalmia-Associated Transcription Factor (MITF) Expression

    OpenAIRE

    Shu-Mei Lee; Yi-Shyan Chen; Chih-Chien Lin; Kuan-Hung Chen

    2015-01-01

    Hair coloring products are one of the most important cosmetics for modern people; there are three major types of hair dyes, including the temporary, semi-permanent and permanent hair dyes. The selected hair dyes (such as ammonium persulfate, sodium persulfate, resorcinol and lawsone) are the important components for hair coloring products. Therefore, we analyzed the effects of these compounds on melanogenesis in B16-F10 melanoma cells. The results proved that hair dyes resorcinol and lawsone ...

  18. Melanoma immunotherapy dominates the field.

    Science.gov (United States)

    Diamantopoulos, Panagiotis; Gogas, Helen

    2016-07-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:27563656

  19. The effect of low-level laser irradiation (In-Ga-Al-AsP - 660 nm on melanoma in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Bjordal Jan M

    2009-11-01

    Full Text Available Abstract Background It has been speculated that the biostimulatory effect of Low Level Laser Therapy could cause undesirable enhancement of tumor growth in neoplastic diseases. The aim of the present study is to analyze the behavior of melanoma cells (B16F10 in vitro and the in vivo development of melanoma in mice after laser irradiation. Methods We performed a controlled in vitro study on B16F10 melanoma cells to investigate cell viability and cell cycle changes by the Tripan Blue, MTT and cell quest histogram tests at 24, 48 and 72 h post irradiation. The in vivo mouse model (male Balb C, n = 21 of melanoma was used to analyze tumor volume and histological characteristics. Laser irradiation was performed three times (once a day for three consecutive days with a 660 nm 50 mW CW laser, beam spot size 2 mm2, irradiance 2.5 W/cm2 and irradiation times of 60s (dose 150 J/cm2 and 420s (dose 1050 J/cm2 respectively. Results There were no statistically significant differences between the in vitro groups, except for an increase in the hypodiploid melanoma cells (8.48 ± 1.40% and 4.26 ± 0.60% at 72 h post-irradiation. This cancer-protective effect was not reproduced in the in vivo experiment where outcome measures for the 150 J/cm2 dose group were not significantly different from controls. For the 1050 J/cm2 dose group, there were significant increases in tumor volume, blood vessels and cell abnormalities compared to the other groups. Conclusion LLLT Irradiation should be avoided over melanomas as the combination of high irradiance (2.5 W/cm2 and high dose (1050 J/cm2 significantly increases melanoma tumor growth in vivo.

  20. The effect of low-level laser irradiation (In-Ga-Al-AsP - 660 nm) on melanoma in vitro and in vivo

    International Nuclear Information System (INIS)

    It has been speculated that the biostimulatory effect of Low Level Laser Therapy could cause undesirable enhancement of tumor growth in neoplastic diseases. The aim of the present study is to analyze the behavior of melanoma cells (B16F10) in vitro and the in vivo development of melanoma in mice after laser irradiation. We performed a controlled in vitro study on B16F10 melanoma cells to investigate cell viability and cell cycle changes by the Tripan Blue, MTT and cell quest histogram tests at 24, 48 and 72 h post irradiation. The in vivo mouse model (male Balb C, n = 21) of melanoma was used to analyze tumor volume and histological characteristics. Laser irradiation was performed three times (once a day for three consecutive days) with a 660 nm 50 mW CW laser, beam spot size 2 mm2, irradiance 2.5 W/cm2 and irradiation times of 60s (dose 150 J/cm2) and 420s (dose 1050 J/cm2) respectively. There were no statistically significant differences between the in vitro groups, except for an increase in the hypodiploid melanoma cells (8.48 ± 1.40% and 4.26 ± 0.60%) at 72 h post-irradiation. This cancer-protective effect was not reproduced in the in vivo experiment where outcome measures for the 150 J/cm2 dose group were not significantly different from controls. For the 1050 J/cm2 dose group, there were significant increases in tumor volume, blood vessels and cell abnormalities compared to the other groups. LLLT Irradiation should be avoided over melanomas as the combination of high irradiance (2.5 W/cm2) and high dose (1050 J/cm2) significantly increases melanoma tumor growth in vivo

  1. Transplant rejection

    Science.gov (United States)

    ... is usually not perfect. No two people, except identical twins, have identical tissue antigens. Doctors use medicines to ... has no blood supply. Also, transplants from one identical twin to another are almost never rejected. There are ...

  2. Organ Transplantation

    Science.gov (United States)

    ... their death. One strategy is simply to permit organ sale by changing the National Organ Transplant Act (NOTA), the federal law that bans organ sales. Then, individuals would be free to broker contracts ...

  3. Liver Transplantation

    Science.gov (United States)

    ... to follow a treatment regimen a lack of psychosocial support In addition, the transplant candidate may decide ... is a challenging and complex surgery with significant risks to the donor, including death. According to the ...

  4. Lung transplant

    Science.gov (United States)

    ... diseases that may require a lung transplant are: Cystic fibrosis Damage to the arteries of the lung because ... BC; Clinical Practice Guidelines for Pulmonary Therapies Committee; Cystic Fibrosis Foundation Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: ...

  5. Pancreas Transplantation

    Science.gov (United States)

    The pancreas is a gland behind your stomach and in front of your spine. It produces the juices that ... hormones that help control blood sugar levels. A pancreas transplant is surgery to place a healthy pancreas ...

  6. Kidney transplant

    Science.gov (United States)

    ... Heart tests such as an EKG, echocardiogram, or cardiac catheterization Tests to look for early cancer You will also want to consider one or more transplant centers to determine which is best for you. ...

  7. Pancreas transplant

    Science.gov (United States)

    ... Heart tests such as an EKG, echocardiogram, or cardiac catheterization Tests to look for early cancer You will also want to consider one or more transplant centers to determine which is best for you: ...

  8. Corneal transplant

    Science.gov (United States)

    ... clear outer lens on the front of the eye. A corneal transplant is surgery to replace the cornea with tissue ... years. Rejection can sometimes be controlled with steroid eye drops. Other ... are: Bleeding Cataracts Infection of the eye Glaucoma ( ...

  9. Melanoma Lentiginoso Acral

    Directory of Open Access Journals (Sweden)

    Gloria Andrea Vargas Suaza

    2008-12-01

    Full Text Available El melanoma lentiginoso acral (MLA es una variante rápidamente progresiva del melanoma maligno (MM. Constituye el 5-10% de todos los tipos de MM y se presenta con mayor frecuencia en pacientes de raza negra, asiáticos y latinoamericanos. En Colombia el MM se encuentra en aumento, con una incidencia de 3.5/100.000, siendo el MLA una de las variantes más comunes. La edad promedio de presentación es de 58 años, con una tasa de sobrevida menor para las personas de raza negra, asociado a un diagnóstico tardío. EL MLA se localiza en plantas, palmas y región subungueal y en su etiopatología se ha descrito la presencia de mutaciones en genes: 9p21 (p16: 67%, 11q13 (CCND1 (47%, 22q11-q13 (40% y 5p15 (20%. El diagnóstico de MLA, se ha fundamentado clásicamente en la histopatología. Herramientas de diagnóstico como la dermatoscopia, la evaluación del ganglio centinela y la determinación de alteraciones en las proteínas del ciclo celular contribuyen a la detección precoz del MLA y el MM en general.

  10. Morphogenesis of early stage melanoma

    Science.gov (United States)

    Chatelain, Clément; Amar, Martine Ben

    2015-08-01

    Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

  11. METASTATIC MALIGNANT MELANOMA: CASE REPORT

    Directory of Open Access Journals (Sweden)

    Satish

    2015-06-01

    Full Text Available A 32 year s old man presented with well - defined lesion on the left sole 8 months back. Biopsy and FNAC from the lesion confirmed malignant melanoma left foot & the patient was advised excision. After 4 months patient gave h/o swelling on the medial aspect of the thigh. The patient was diagnosed to have fulminant metastatic malignant melanoma of the left foot with metastasis to femoral lymph node. This case report re - emphasizes the importance of the combined approach to ascertain diagnose early KEYWORDS : Melanoma .

  12. Uveal Melanoma UK National Guidelines.

    Science.gov (United States)

    Nathan, P; Cohen, V; Coupland, S; Curtis, K; Damato, B; Evans, J; Fenwick, S; Kirkpatrick, L; Li, O; Marshall, E; McGuirk, K; Ottensmeier, C; Pearce, N; Salvi, S; Stedman, B; Szlosarek, P; Turnbull, N

    2015-11-01

    The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website. PMID:26278648

  13. Effects of Qingban Capsules on Melanin Synthesis of Murine B16 Cells%大豆异黄酮清斑软胶囊对小鼠B16细胞黑色素合成的影响

    Institute of Scientific and Technical Information of China (English)

    张国栋; 黄恺飞; 黄亦琦

    2012-01-01

    目的 测定大豆异黄酮清斑软胶囊对小鼠B16细胞黑色素合成的影响,研究其对黄褐斑的治疗作用. 方法 小鼠B16黑素细胞作为受试细胞,选择氢醌作为阳性对照物,用MTT比色法测定药物对细胞增殖的影响,采用酶学方法检测对酪氨酸酶活性的影响,NaOH溶解法测定黑素含量. 结果 不同浓度大豆异黄酮清斑软胶囊对黑素细胞增殖、酪氨酸酶活性及黑色素含量均有抑制作用,呈现剂量依赖性关系. 结论 大豆异黄酮清斑软胶囊能有效抑制黑素细胞增殖和降低酪氨酸酶活性,从而减少黑素合成.

  14. Kita driven expression of oncogenic HRAS leads to early onset and highly penetrant melanoma in zebrafish.

    Directory of Open Access Journals (Sweden)

    Cristina Santoriello

    Full Text Available BACKGROUND: Melanoma is the most aggressive and lethal form of skin cancer. Because of the increasing incidence and high lethality of melanoma, animal models for continuously observing melanoma formation and progression as well as for testing pharmacological agents are needed. METHODOLOGY AND PRINCIPAL FINDINGS: Using the combinatorial Gal4-UAS system, we have developed a zebrafish transgenic line that expresses oncogenic HRAS under the kita promoter. Already at 3 days transgenic kita-GFP-RAS larvae show a hyper-pigmentation phenotype as earliest evidence of abnormal melanocyte growth. By 2-4 weeks, masses of transformed melanocytes form in the tail stalk of the majority of kita-GFP-RAS transgenic fish. The adult tumors evident between 1-3 months of age faithfully reproduce the immunological, histological and molecular phenotypes of human melanoma, but on a condensed time-line. Furthermore, they show transplantability, dependence on mitfa expression and do not require additional mutations in tumor suppressors. In contrast to kita expressing melanocyte progenitors that efficiently develop melanoma, mitfa expressing progenitors in a second Gal4-driver line were 4 times less efficient in developing melanoma during the three months observation period. CONCLUSIONS AND SIGNIFICANCE: This indicates that zebrafish kita promoter is a powerful tool for driving oncogene expression in the right cells and at the right level to induce early onset melanoma in the presence of tumor suppressors. Thus our zebrafish model provides a link between kita expressing melanocyte progenitors and melanoma and offers the advantage of a larval phenotype suitable for large scale drug and genetic modifier screens.

  15. Tamoxifen inhibits tumor cell invasion and metastasis in mouse melanoma through suppression of PKC/MEK/ERK and PKC/PI3K/Akt pathways

    Energy Technology Data Exchange (ETDEWEB)

    Matsuoka, Hiroshi [Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka 577-8502 (Japan); Department of Pharmacy, Nara Hospital, Kinki University School of Medicine, 1248-1 Ikoma, Nara 630-0293 (Japan); Tsubaki, Masanobu [Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka 577-8502 (Japan); Yamazoe, Yuzuru [Department of Pharmacy, Kinki University Hospital, Osakasayama, Osaka 589-8511 (Japan); Ogaki, Mitsuhiko [Department of Pharmacy, Higahiosaka City General Hospital, Higashi-osaka, Osaka 578-8588 (Japan); Satou, Takao; Itoh, Tatsuki [Department of Pathology, Kinki University School of Medicine, Osakasayama, Osaka 589-8511 (Japan); Kusunoki, Takashi [Department of Otolaryngology, Juntendo University School of Medicine, Tokyo (Japan); Nishida, Shozo, E-mail: nishida@phar.kindai.ac.jp [Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka 577-8502 (Japan)

    2009-07-15

    In melanoma, several signaling pathways are constitutively activated. Among these, the protein kinase C (PKC) signaling pathways are activated through multiple signal transduction molecules and appear to play major roles in melanoma progression. Recently, it has been reported that tamoxifen, an anti-estrogen reagent, inhibits PKC signaling in estrogen-negative and estrogen-independent cancer cell lines. Thus, we investigated whether tamoxifen inhibited tumor cell invasion and metastasis in mouse melanoma cell line B16BL6. Tamoxifen significantly inhibited lung metastasis, cell migration, and invasion at concentrations that did not show anti-proliferative effects on B16BL6 cells. Tamoxifen also inhibited the mRNA expressions and protein activities of matrix metalloproteinases (MMPs). Furthermore, tamoxifen suppressed phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt through the inhibition of PKC{alpha} and PKC{delta} phosphorylation. However, other signal transduction factor, such as p38 mitogen-activated protein kinase (p38MAPK) was unaffected. The results indicate that tamoxifen suppresses the PKC/mitogen-activated protein kinase kinase (MEK)/ERK and PKC/phosphatidylinositol-3 kinase (PI3K)/Akt pathways, thereby inhibiting B16BL6 cell migration, invasion, and metastasis. Moreover, tamoxifen markedly inhibited not only developing but also clinically evident metastasis. These findings suggest that tamoxifen has potential clinical applications for the treatment of tumor cell metastasis.

  16. Melanoma Surveillance in the US: The Economic Burden of Melanoma

    Centers for Disease Control (CDC) Podcasts

    2011-10-19

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Dr. Gery Guy, from the CDC’s Division of Cancer Prevention and Control, discusses the economic burden of melanoma.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

  17. Establishment of mouse CXCR3 gene-transfected cell line B16-mCXCR3 and study of its migration and oncogenic function in vitro and in vivo%转染小鼠CXCR3基因的B16-mCXCR3细胞在体内外迁移和致瘤作用研究

    Institute of Scientific and Technical Information of China (English)

    郭静雅; 朱华亭; 陈昌友; 黄莉; 刘玉华; 孙杰; 张彦军; 黄赛男; 邱玉华

    2011-01-01

    目的:建立稳定表达小鼠CXCR3基因的B16细胞株,研究CXCR3分子在肿瘤形成及转移过程中的作用.方法:采用PCR方法从pMD19-T/mCXCR3质粒中扩增CXCR3基因,插入到真核表达载体pIRES2-EGFP中,脂质体法转染小鼠黑色素瘤细胞B16;G418加压筛选阳性克隆,分别用RT-PCR方法与免疫荧光技术分析阳性克隆中CXCR3在mRNA和蛋白水平的表达.采用Transwell系统检测B16-mCXCR3细胞在其配体IP-10介导下的迁移能力.将B16-mCXCR3细胞分别通过皮下和眼静脉注射接种于BALB/c小鼠,观察在小鼠体内的成瘤率及肿瘤转移情况.结果:构建了表达小鼠CXCR3基因的真核表达载体pIRES2-EGFP/mCXCR3,转染该载体后获得了稳定表达CXCR3的B16-mCXCR3细胞.B16-mCXCR3细胞(1×105个),在20 ìg/L IP-10作用下迁移的细胞数为3 208个,与B16组和B16-mock组相比均具有统计学意义(P<0.01).于小鼠皮下接种B16-mCXCR3细胞、B16细胞和B16-mock细胞,第20天成瘤率均为100%.于小鼠眼静脉注射B16-mCXCR3细胞,第21天时50%的小鼠在肺部出现肉眼可见的黑色肿瘤转移灶,B16细胞组和B16-mock细胞组肺部未见肿瘤转移灶,B16-mCXCR3组与B16组和B16-mock组相比均具有统计学意义(P<0.01).结论:转染CXCR3基因的B16-mCXCR3细胞,在IP-10介导下可定向迁移,并可增加在小鼠体内的转移率.%Objective: In order to investigate the role of mouse gene CXCR3 in the process of tumor formation and metastasis, to construct an engineered B16 cell line expressing the mouse CXCR3 gene constantly.Methods: The eukaryotic transfer vector pIRES2-EGFP-mCXCB3 used to transfect B16 cells was constructed by inserting the PCR-amplified CXCR3 cassette from the plasmid pMD19-T/mCXCR3 between the EcoR I and BamH I sites of the eukaryotic expression vector pIRES2-EGFP and then the transfer vector was transfected into B16 cells by the liposome-mediated methods.The positive B16-mCXCR3 clones were screened for G418-resistance and

  18. International Transplant Nurses Society

    Science.gov (United States)

    ... 25th Annual ITNS Symposium The International Transplant Nurses Society (ITNS) cordially invites transplant nurses and other transplant ... pocket guide, developed by the International Transplant Nurses Society (ITNS), provides an overview of the interventions used ...

  19. American Society of Transplantation

    Science.gov (United States)

    ... Trials in Transplantation September 13, 2016 The American Society of Transplantation and its Transplantation & Immunology Research Network ... Learn More Donate Donate Donate to the American Society of Transplantation Advertisement member spotlight View all Joanna ...

  20. Transplant Program Reports

    Science.gov (United States)

    ... Find a Transplant Center The SRTR transplant program reports include: Reliable transplant information for patients, families, and ... statistics To retrieve the most recent transplant program reports, please click on an organ type in the ...

  1. The association of N-palmitoylethanolamine with the FAAH inhibitor URB597 impairs melanoma growth through a supra-additive action

    International Nuclear Information System (INIS)

    The incidence of melanoma is considerably increasing worldwide. Frequent failing of classical treatments led to development of novel therapeutic strategies aiming at managing advanced forms of this skin cancer. Additionally, the implication of the endocannabinoid system in malignancy is actively investigated. We investigated the cytotoxicity of endocannabinoids and their hydrolysis inhibitors on the murine B16 melanoma cell line using a MTT test. Enzyme and receptor expression was measured by RT-PCR and enzymatic degradation of endocannabinoids using radiolabeled substrates. Cell death was assessed by Annexin-V/Propidium iodine staining. Tumors were induced in C57BL/6 mice by s.c. flank injection of B16 melanoma cells. Mice were injected i.p. for six days with vehicle or treatment, and tumor size was measured each day and weighted at the end of the treatment. Haematoxylin-Eosin staining and TUNEL assay were performed to quantify necrosis and apoptosis in the tumor and endocannabinoid levels were quantified by HPLC-MS. Tube formation assay and CD31 immunostaining were used to evaluate the antiangiogenic effects of the treatments. The N-arachidonoylethanolamine (anandamide, AEA), 2-arachidonoylglycerol and N- palmitoylethanolamine (PEA) reduced viability of B16 cells. The association of PEA with the fatty acid amide hydrolase (FAAH) inhibitor URB597 considerably reduced cell viability consequently to an inhibition of PEA hydrolysis and an increase of PEA levels. The increase of cell death observed with this combination of molecules was confirmed in vivo where only co-treatment with both PEA and URB597 led to decreased melanoma progression. The antiproliferative action of the treatment was associated with an elevation of PEA levels and larger necrotic regions in the tumor. This study suggests the interest of targeting the endocannabinoid system in the management of skin cancer and underlines the advantage of associating endocannabinoids with enzymatic hydrolysis

  2. High accuracy of family history of melanoma in Danish melanoma cases

    DEFF Research Database (Denmark)

    Wadt, Karin A W; Drzewiecki, Krzysztof T; Gerdes, Anne-Marie

    2015-01-01

    The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor but...... previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma...... probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77% of all relatives, and in 83% of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree...

  3. Idiopathic Organ Transplant Chorioretinopathy after Liver Transplantation

    OpenAIRE

    Maria Fernanda Abalem; Pedro Carlos Carricondo; Sergio Luis Gianotti Pimentel; Walter Yukihiko Takahashi

    2015-01-01

    Idiopathic organ transplant chorioretinopathy is a rare disease associated with kidney and heart transplantation. We present a case secondary to liver transplantation including its multimodal imaging, differential diagnosis, and physiopathology discussion.

  4. The Complement C3a Receptor Contributes to Melanoma Tumorigenesis by Inhibiting Neutrophil and CD4+ T Cell Responses.

    Science.gov (United States)

    Nabizadeh, Jamileh A; Manthey, Helga D; Steyn, Frederik J; Chen, Weiyu; Widiapradja, Alexander; Md Akhir, Fazrena N; Boyle, Glen M; Taylor, Stephen M; Woodruff, Trent M; Rolfe, Barbara E

    2016-06-01

    The complement peptide C3a is a key component of the innate immune system and a major fragment produced following complement activation. We used a murine model of melanoma (B16-F0) to identify a hitherto unknown role for C3a-C3aR signaling in promoting tumor growth. The results show that the development and growth of B16-F0 melanomas is retarded in mice lacking C3aR, whereas growth of established melanomas can be arrested by C3aR antagonism. Flow cytometric analysis showed alterations in tumor-infiltrating leukocytes in the absence of C3aR. Specifically, neutrophils and CD4(+) T lymphocyte subpopulations were increased, whereas macrophages were reduced. The central role of neutrophils was confirmed by depletion experiments that reversed the tumor inhibitory effects observed in C3aR-deficient mice and returned tumor-infiltrating CD4(+) T cells to control levels. Analysis of the tumor microenvironment showed upregulation of inflammatory genes that may contribute to the enhanced antitumor response observed in C3aR-deficient mice. C3aR deficiency/inhibition was also protective in murine models of BRAF(V600E) mutant melanoma and colon and breast cancer, suggesting a tumor-promoting role for C3aR signaling in a range of tumor types. We propose that C3aR activation alters the tumor inflammatory milieu, thereby promoting tumor growth. Therapeutic inhibition of C3aR may therefore be an effective means to trigger an antitumor response in melanoma and other cancers. PMID:27183625

  5. Malignant melanoma of the vulva

    OpenAIRE

    Ragnarsson Olding, Boel

    1999-01-01

    From a consecutive, nationwide series of 219 females with primary vulvar malignant melanomas diagnosed in Sweden during 1960 to 1984 and followed up until 1994, we analyzed epidemiological, clinical, histopathological, prognostic and molecular genetic data. The age-standardized incidence among these patients, 75 % of whom were 60 years old or more, decreased by 3.2 % annually compared to an increase of almost 6 % for contemporary cutaneous melanomas in Sweden. Relative 5-and...

  6. Perceived Intra-Family Melanoma Risk Communication

    OpenAIRE

    Loescher, Lois J.; Crist, Janice D.; Siaki, Leilani A.C.L.

    2009-01-01

    Melanoma is a skin cancer that can be deadly. Members of families with a strong history of melanoma have a high risk of melanoma occurrence or recurrence. Enhanced survival in these family members could be influenced by their knowledge of melanoma risk and by simple behaviors to decrease their risk or detect melanoma in its early, most curable, stage. Yet, there is minimal exploration on communication of risk or risk-modifying behaviors in melanoma at-risk families. In this study we described...

  7. Efficacy of Re-188-labelled sulphur colloid on prolongation of survival time in melanoma-bearing animals

    International Nuclear Information System (INIS)

    In this study, the effectiveness of a 188Re labeled sulfur colloid with two particle size ranges was used to evaluate the effectiveness of this agent on melanoma tumors in mice in terms of animal lifespan. Methods: Two separate group of animals were used for investigating biodistribution and survival time. A total of 188 B16F10-melanoma-bearing BDF1 mice were injected intraperitoneally with 3.7 MBq (0.1mCi)/2mL of radiolabeled sulfur colloid ten days after intraperitoneal inoculation of 5x105 B16F10 melanoma cells/2ml. For group 1, 30 mice were sacrificed at 1, 4, 24, 48 and 72 hours for biodistribution studies. In group 2, 158 mice were divided into 9 groups (n=16∼18/groups)each receiving respectively tumor alone, tumor with normal saline, cold colloid or hot colloid with 16, 23, 31, 46, 62, or 124 MBq activity. Each of these colloid groups was further divided into two groups, one receiving smaller particle sizes (188Re-sulfur colloid is an effective agent in controlling tumor cells in the abdominal cavity in animals

  8. Coating Solid Lipid Nanoparticles with Hyaluronic Acid Enhances Antitumor Activity against Melanoma Stem-like Cells

    Science.gov (United States)

    Shen, Hongxin; Shi, Sanjun; Zhang, Zhirong; Gong, Tao; Sun, Xun

    2015-01-01

    Successful anticancer chemotherapy requires targeting tumors efficiently and further potential to eliminate cancer stem cell (CSC) subpopulations. Since CD44 is present on many types of CSCs, and it binds specially to hyaluronic acid (HA), we tested whether coating solid lipid nanoparticles with hyaluronan (HA-SLNs)would allow targeted delivery of paclitaxel (PTX) to CD44-overexpressing B16F10 melanoma cells. First, we developed a model system based on melanoma stem-like cells for experiments in vitro and in mouse xenografts, and we showed that cells expressing high levels of CD44 (CD44+) displayed a strong CSC phenotype while cells expressing low levels of CD44 (CD44-) did not. This phenotype included sphere and colony formation, higher proportion of side population cells, expression of CSC-related markers (ALDH, CD133, Oct-4) and tumorigenicity in vivo. Next we showed that administering PTX-loaded HA-SLNs led to efficient intracellular delivery of PTX and induced substantial apoptosis in CD44+ cells in vitro. In the B16F10-CD44+ lung metastasis model, PTX-loaded HA-SLNs targeted the tumor-bearing lung tissues well and subsequently exhibited significant antitumor effects with a relative low dose of PTX, which provided significant survival benefit without evidence of adverse events. These findings suggest that the HA-SLNs targeting system shows promise for enhancing cancer therapy. PMID:25897340

  9. Characterization and Inducing Melanoma Cell Apoptosis Activity of Mannosylerythritol Lipids-A Produced from Pseudozyma aphidis.

    Science.gov (United States)

    Fan, Linlin; Li, Hongji; Niu, Yongwu; Chen, Qihe

    2016-01-01

    Mannosylerythritol lipids (MELs) are natural glycolipid biosurfactants which have potential applications in the fields of food, cosmetic and medicine. In this study, MELs were produced from vegetable oil by Pseudozyma aphidis. Their structural data through LC/MS, GC/MS and NMR analysis revealed that MEL-A with two acetyls was the major compound and the identified homologs of MEL-A contained a length of C8 to C14 fatty acid chains. This glycolipid exhibited a surface tension of 27.69 mN/m at a critical micelle concentration (CMC), self-assembling into particles in the water solution. It was observed to induce cell growth-inhibition and apoptosis of B16 melanoma cells in a dose-dependent manner, as well as cause cell cycle arrest at the S phase. Further quantitative RT-PCR analysis and western blotting revealed an increasing tendency of both mRNA and protein expressions of Caspase-12, CHOP, GRP78 and Caspase-3, and a down-regulation of protein Bcl-2. Combined with the up regulation of signaling IRE1 and ATF6, it can be speculated that MEL-A-induced B16 melanoma cell apoptosis was associated with the endoplasmic reticulum stress (ERS). PMID:26828792

  10. In vitro incorporation of boronophenylalanine by amelanotic and melanotic murine and human malignant melanoma cell lines

    International Nuclear Information System (INIS)

    Pelleted cells were irradiated as previously described, following a 20 h incubation in RPM1 1640 medium, in the presence or absence of 10μg/ml D,L-paraboronophenylalanine hydrochloride (10B1-BPA.HCl). Thermal neutrons were derived from Moata, a 100-kW Argonaut-type light water reactor. The neutron flux was 2.6 x 109 n/cm2/s, dose rate 3.7 Gy/h (n+γ) and the dose range 0.6 - 0.8 Gy. Cells were plated onto X-irradiated feeder layers in triplicate in 25cm2 Falcon flasks and colonies counted after 11-12 days. No differences in thermal neutron radiosensitivity were observed for two amelanotic cell lines. A small but significant difference was observed for the melanotic cell line (418) grown in the presence or absence of BPA. Subsequent experiments showed that the uptake of boron was low in the B16 murine malignant melanoma cell line cultured in the presence of BPA. It was therefore necessary to investigate the boron uptake and incorporation in melanoma cells by increasing the BPA concentration, increasing melanization using different variants of the B16 cell lines, and alternative methods of cell layer detachment

  11. Effect of long-wave UV radiation on mouse melanoma: An in vitro and in vivo study

    International Nuclear Information System (INIS)

    doses of UVA irradiation. This enhancement of adhesiveness might lead to an increase in binding tumor cells to the endothelial lining of vasculature in various internal organs if occurring also in vivo. A further novel observation is that UVA induced both decline in the expression of E-cadherin adhesion molecule and increase in the expression of the N-cadherin adhesion molecule. In addition, a significant decline in homotypic melanoma-melanoma adhesion (clustering) was observed, which might result in the reduction of E-cadherin expression. It appears that UVA irradiation might reduce melanoma-melanoma interaction through decreasing the expression of E-cadherin and simultaneously enhance the adhesiveness of melanoma cells to endothelium, which in part could be mediated by N-cadherin expression. The aim of the in vivo animal study was to confirm the physiological significance of previously obtained in vitro results and to determine whether UVA radiation might increase melanoma metastasis in vivo. The use of C57BL/6 mice and syngeneic melanoma cell lines B16-F1 and B16-F10 showed that mice, which were i.v. injected with B16-F1 melanoma cells and thereafter exposed to UVA developed significantly more lung metastases when compared with the non-UVA-exposed group. To study the mechanism behind this phenomenon, the direct effect of UVA-induced lung colonization capacity was examined by the in vitro exposure of B16-F1 cells. Alternatively, the UVA-induced immunosuppression, which might be involved in increased melanoma metastasis, was measured by standard contact hypersensitivity assay (CHS). It appears that the UVA-induced increase of metastasis in vivo might be caused by a combination of UVA-induced systemic immunosuppression, and to the lesser extent, it might be caused by the increased adhesiveness of UVA irradiated melanoma cells. Finally, the UVA effect on gene expression in mouse melanoma was determined by a cDNA array, which revealed UVA-induced changes in the 9

  12. Effect of long-wave UV radiation on mouse melanoma: An in vitro and in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Pastila, R.

    2006-04-15

    doses of UVA irradiation. This enhancement of adhesiveness might lead to an increase in binding tumor cells to the endothelial lining of vasculature in various internal organs if occurring also in vivo. A further novel observation is that UVA induced both decline in the expression of E-cadherin adhesion molecule and increase in the expression of the N-cadherin adhesion molecule. In addition, a significant decline in homotypic melanoma-melanoma adhesion (clustering) was observed, which might result in the reduction of E-cadherin expression. It appears that UVA irradiation might reduce melanoma-melanoma interaction through decreasing the expression of E-cadherin and simultaneously enhance the adhesiveness of melanoma cells to endothelium, which in part could be mediated by N-cadherin expression. The aim of the in vivo animal study was to confirm the physiological significance of previously obtained in vitro results and to determine whether UVA radiation might increase melanoma metastasis in vivo. The use of C57BL/6 mice and syngeneic melanoma cell lines B16-F1 and B16-F10 showed that mice, which were i.v. injected with B16-F1 melanoma cells and thereafter exposed to UVA developed significantly more lung metastases when compared with the non-UVA-exposed group. To study the mechanism behind this phenomenon, the direct effect of UVA-induced lung colonization capacity was examined by the in vitro exposure of B16-F1 cells. Alternatively, the UVA-induced immunosuppression, which might be involved in increased melanoma metastasis, was measured by standard contact hypersensitivity assay (CHS). It appears that the UVA-induced increase of metastasis in vivo might be caused by a combination of UVA-induced systemic immunosuppression, and to the lesser extent, it might be caused by the increased adhesiveness of UVA irradiated melanoma cells. Finally, the UVA effect on gene expression in mouse melanoma was determined by a cDNA array, which revealed UVA-induced changes in the 9

  13. Ultra-structural cell distribution of the melanoma marker iodobenzamide: improved potentiality of SIMS imaging in life sciences

    Directory of Open Access Journals (Sweden)

    Papon Janine

    2004-04-01

    Full Text Available Abstract Background Analytical imaging by secondary ion mass spectrometry (SIMS provides images representative of the distribution of a specific ion within a sample surface. For the last fifteen years, concerted collaborative research to design a new ion microprobe with high technical standards in both mass and lateral resolution as well as in sensitivity has led to the CAMECA NanoSims 50, recently introduced onto the market. This instrument has decisive capabilities, which allow biological applications of SIMS microscopy at a level previously inaccessible. Its potential is illustrated here by the demonstration of the specific affinity of a melanoma marker for melanin. This finding is of great importance for the diagnosis and/or treatment of malignant melanoma, a tumour whose worldwide incidence is continuously growing. Methods The characteristics of the instrument are briefly described and an example of application is given. This example deals with the intracellular localization of an iodo-benzamide used as a diagnostic tool for the scintigraphic detection of melanic cells (e.g. metastasis of malignant melanoma. B16 melanoma cells were injected intravenously to C57BL6/J1/co mice. Multiple B16 melanoma colonies developed in the lungs of treated animals within three weeks. Iodobenzamide was injected intravenously in tumour bearing mice six hours before sacrifice. Small pieces of lung were prepared for SIMS analysis. Results Mouse lung B16 melanoma colonies were observed with high lateral resolution. Cyanide ions gave "histological" images of the cell, representative of the distribution of C and N containing molecules (e.g. proteins, nucleic acids, melanin, etc. while phosphorus ions are mainly produced by nucleic acids. Iodine was detected only in melanosomes, confirming the specific affinity of the drug for melanin. No drug was found in normal lung tissue. Conclusion This study demonstrates the potential of SIMS microscopy, which allows the

  14. Preliminary biological evaluation of acridinic compounds for a targeted combined chemo and internal radionuclide therapy for melanoma

    International Nuclear Information System (INIS)

    The increasing incidence of melanoma and a lack of effective therapy on the disseminated form induces the development of selective tissue-targeted therapies. The aim of the present work was a targeting approach combining a bimodality therapy with the same compound exhibiting both chemo and internal radionuclide therapeutic properties. Benzamides are known to present a specific affinity for melanoma tissue. Former studies have shown that with aromatic and hetero-aromatic analogues of N-(2-diethylaminoethyl)- 4-iodo benzamide (B.Z.A.), the affinity for melanoma was maintained. In this context, new compounds have been designed and synthesized conjugating a cytotoxic hetero-aromatic moiety, an amino-alkyl amidic side chain for melanoma targeting and a radioiodine for internal radionuclide therapy. Acridinic derivatives known as cytotoxic DNA-intercalating agents have been chosen for this study. The cytotoxic activity of fifteen new compounds has been tested in vitro on a panel of cell lines and the I.C.50 values were determined. The three first selected compounds have been further evaluated: in vivo, on B 16 F0 melanoma bearing C 57 B.L.6 mice to determine the pharmacological kinetic and namely the tumoral affinity. Two compounds exhibited a high, specific and long lasting concentration in melanoma tumor giving them a kinetic profile favourable for an application to radionuclide therapy; in vitro, using the 'colony forming' test on melanoma cells, for a first approach of association of chemo toxicity and radiotoxicity. Assessed on the ability of cells to form colonies, the inhibition observed with the association for a same molecule of chemo toxic and radio toxic doses was quite exactly the sum of the two separate effects, a result providing a first validation of the radio chemotherapy concept; in vitro, by a preliminary determination of molecular mechanisms. Compared to parent compounds, results confirmed a maintain of DNA-intercalating properties. These first results

  15. Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma.

    Science.gov (United States)

    Spain, L; Higgins, R; Gopalakrishnan, K; Turajlic, S; Gore, M; Larkin, J

    2016-06-01

    Immune checkpoint inhibitors such as ipilimumab and nivolumab improve survival in patients with advanced melanoma and are increasingly available to clinicians for use in the clinic. Their safety in organ transplant recipients is not well defined but published case reports describing treatment with ipilimumab have not been complicated by graft rejection. No cases of anti-programmed cell death protein 1 administration are reported in this group. We describe a case of acute graft rejection in a kidney transplant recipient after treatment with nivolumab, after progression on ipilimumab. Potential factors increasing the risk of graft rejection in this case are discussed, in particular the contribution of nivolumab. PMID:26951628

  16. Protein engineering of insulin: Two novel fast-acting insulins [B16Ala]insulin and [B26Ala]insulin

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Zhou; (张舟); TANG; Yuehua; (唐月华); YAO; Shiyin; (姚矢音); ZHU; Shangquan; (朱尚权); FENG; Youmin; (冯佑民)

    2003-01-01

    Blood glucose lowering assay proved that [B16Ala]insulin and [B26Ala]insulin exhibit potency of acute blood glucose lowering in normal pigs, which demonstrates that they are fast- acting insulin. Single-chain precursor of [B16Ala]insulin and [B26Ala]insulin is [B16Ala]PIP and [B26Ala]PIP, respectively, which are suitable for gene expression. Secretory expression level of the precursors in methylotrophic yeast Pichia pastoris was quite high, 650 mg/L and 130 mg/L, respectively. In vivo biological assay showed that the two fast-acting insulins have full or nearly full biological activity. So both [B16Ala]insulin and [B26Ala]insulin can be well developed as fast-acting insulin for clinic use.

  17. A/C magnetic hyperthermia of melanoma mediated by iron(0)/iron oxide core/shell magnetic nanoparticles: a mouse study

    International Nuclear Information System (INIS)

    There is renewed interest in magnetic hyperthermia as a treatment modality for cancer, especially when it is combined with other more traditional therapeutic approaches, such as the co-delivery of anticancer drugs or photodynamic therapy. The influence of bimagnetic nanoparticles (MNPs) combined with short external alternating magnetic field (AMF) exposure on the growth of subcutaneous mouse melanomas (B16-F10) was evaluated. Bimagnetic Fe/Fe3O4 core/shell nanoparticles were designed for cancer targeting after intratumoral or intravenous administration. Their inorganic center was protected against rapid biocorrosion by organic dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin) units were attached to the dopamine-oligoethylene glycol ligands. The magnetic hyperthermia results obtained after intratumoral injection indicated that micromolar concentrations of iron given within the modified core-shell Fe/Fe3O4 nanoparticles caused a significant anti-tumor effect on murine B16-F10 melanoma with three short 10-minute AMF exposures. We also observed a decrease in tumor size after intravenous administration of the MNPs followed by three consecutive days of AMF exposure 24 hrs after the MNPs injection. These results indicate that intratumoral administration of surface modified MNPs can attenuate mouse melanoma after AMF exposure. Moreover, we have found that after intravenous administration of micromolar concentrations, these MNPs are capable of causing an anti-tumor effect in a mouse melanoma model after only a short AMF exposure time. This is a clear improvement to state of the art

  18. Aldesleukin and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

    Science.gov (United States)

    2016-04-21

    Metastatic Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck

  19. 76 FR 46597 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2A12 (CL-601) and CL-600-2B16 (CL-601-3A...

    Science.gov (United States)

    2011-08-03

    .... Model CL-600-2A12 (CL- 601) and CL-600-2B16 (CL-601-3A, CL-601-3R, and CL-604 Variants) Airplanes... Bombardier, Inc. model-- Task(s)-- Initial compliance time (whichever occurs later)-- CL-600-2A12 (CL-601... icing. accumulation of 4,800 after the effective inclusive; and CL-600-2B16 (CL- total flight hours;...

  20. 76 FR 66203 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B16 (CL-601-3A, CL-601-3R, and CL-604...

    Science.gov (United States)

    2011-10-26

    ... Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant economic.... Model CL-600-2B16 (CL- 601-3A, CL-601-3R, and CL-604 Variants) Airplanes AGENCY: Federal Aviation... Bombardier, Inc. Model CL-600-2B16 (CL- 601-3A, CL-601-3R, and CL-604 Variants) airplanes, certificated...

  1. Corneal Transplantation

    DEFF Research Database (Denmark)

    Hjortdal, Jesper Østergaard

    . Economic considerations on cost and benefi t of medical treatment and surgical procedures are today an integrated part of the health system in many countries, and a chapter covers these aspects of corneal transplantation. This textbook is aimed at presenting an updated review of the new techniques...... with less risk of rejection episodes. Besides covering updated chapters on penetrating keratoplasty, and anterior and posterior lamellar procedures, this textbook also gives a thorough overview of the history of corneal transplantation and a detailed presentation of the microstructural components...

  2. Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [18F]ICF01006, a highly promising melanoma PET tracer

    International Nuclear Information System (INIS)

    Here, we report a new and rapid radiosynthesis of 18F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([18F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. [18F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [18F]ICF01006 were evaluated at different stages of tumoural growth and compared to 18F-fluorodeoxyglucose ([18F]FDG). The fully automated radiosynthesis of [18F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/μmol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [18F]ICF01006 tumoural uptake of 1.64 ± 0.57, 3.40 ± 1.47 and 11.44 ± 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [18F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 ± 2.08 %ID/g (versus 0.41 ± 0.90 %ID/g in control mice). In the two models, comparison with [18F]FDG showed that both radiotracers were able to detect melanoma lesions, but [18F]ICF01006 was superior in terms of contrast and specificity. Our promising results provide further preclinical data, reinforcing the excellent potential of [18F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. (orig.)

  3. Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [{sup 18}F]ICF01006, a highly promising melanoma PET tracer

    Energy Technology Data Exchange (ETDEWEB)

    Rbah-Vidal, Latifa; Vidal, Aurelien; Besse, Sophie; Audin, Laurent; Degoul, Francoise; Miot-Noirault, Elisabeth; Moins, Nicole; Auzeloux, Philippe; Chezal, Jean-Michel [Clermont Universite, Universite d' Auvergne, Imagerie Moleculaire et Therapie Vectorisee, BP 10448, Clermont-Ferrand (France); Inserm, U 990, Clermont-Ferrand (France); Cachin, Florent [Clermont Universite, Universite d' Auvergne, Imagerie Moleculaire et Therapie Vectorisee, BP 10448, Clermont-Ferrand (France); Inserm, U 990, Clermont-Ferrand (France); Centre Jean Perrin, Clermont-Ferrand (France); Bonnet, Mathilde [U1071 INSERM-Universite d' Auvergne, M2USH, Clermont-Ferrand (France); Askienazy, Serge [CYCLOPHARMA Laboratories, Biopole Clermont-Limagne, Saint-Beauzire (France); Dolle, Frederic [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France)

    2012-09-15

    Here, we report a new and rapid radiosynthesis of {sup 18}F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([{sup 18}F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. [{sup 18}F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [{sup 18}F]ICF01006 were evaluated at different stages of tumoural growth and compared to {sup 18}F-fluorodeoxyglucose ([{sup 18}F]FDG). The fully automated radiosynthesis of [{sup 18}F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/{mu}mol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [{sup 18}F]ICF01006 tumoural uptake of 1.64 {+-} 0.57, 3.40 {+-} 1.47 and 11.44 {+-} 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [{sup 18}F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 {+-} 2.08 %ID/g (versus 0.41 {+-} 0.90 %ID/g in control mice). In the two models, comparison with [{sup 18}F]FDG showed that both radiotracers were able to detect melanoma lesions, but [{sup 18}F]ICF01006 was superior in terms of contrast and specificity. Our promising results provide further preclinical data, reinforcing the excellent potential of [{sup 18}F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. (orig.)

  4. Role of Acid Sphingomyelinase-Induced Signaling in Melanoma Cells for Hematogenous Tumor Metastasis

    Directory of Open Access Journals (Sweden)

    Alexander Carpinteiro

    2016-01-01

    Full Text Available Background: Hematogenous metastasis of malignant tumor cells is a multistep process that requires release of tumor cells from the local tumor mass, interaction of the tumor cells with platelets in the blood, and adhesion of either the activated tumor cells or the complexes of platelets and tumor cells to the endothelial cells of the target organ. We have previously shown that the interaction of melanoma cells with platelets results in the release of acid sphingomyelinase (Asm from activated platelets. Secreted platelet-derived Asm acts on malignant tumor cells to cluster and activate integrins; such clustering and activation are necessary for tumor cell adhesion to endothelial cells and for metastasis. Methods: We examined the response of tumor cells to treatment with extracellular sphingomyelinase or co-incubation with wild-type and Asm-deficient platelets. We determined the phosphorylation and activation of several intracellular signaling molecules, in particular p38 kinase (p38K, phospholipase Cγ (PLCγ, ezrin, and extracellular signal-regulated kinases. Results: Incubation of B16F10 melanoma cells with Asm activates p38 MAP kinase (p38K, phospholipase Cγ (PLCγ, ezrin, and extracellular signal-regulated kinases. Co-incubation of B16F10 melanoma cells with wild-type or Asm-deficient platelets showed that the phosphorylation/activation of p38K is dependent on Asm. Pharmacological blockade of p38K prevents activation of β1 integrin and adhesion in vitro. Most importantly, inhibition of p38K activity in B16F10 melanoma cells prevents tumor cell adhesion and metastasis to the lung in vivo, a finding indicating the importance of p38K for metastasis. Conclusions: Asm, secreted from activated platelets after tumor cell-platelet contact, induces p38K phosphorylation in tumor cells. This in turn stimulates β1 integrin activation that is necessary for adhesion and subsequent metastasis of tumor cells. Thus, inhibition of p38K might be a novel

  5. Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes

    International Nuclear Information System (INIS)

    Melanoma is the major cause of skin cancer deaths and melanoma incidence doubles every 10 to 20 years. However, little is known about melanoma pathway aberrations. Here we applied the robust Gene Identification Signature Paired End diTag (GIS-PET) approach to investigate the melanoma transcriptome and characterize the global pathway aberrations. GIS-PET technology directly links 5' mRNA signatures with their corresponding 3' signatures to generate, and then concatenate, PETs for efficient sequencing. We annotated PETs to pathways of KEGG database and compared the murine B16F1 melanoma transcriptome with three non-melanoma murine transcriptomes (Melan-a2 melanocytes, E14 embryonic stem cells, and E17.5 embryo). Gene expression levels as represented by PET counts were compared across melanoma and melanocyte libraries to identify the most significantly altered pathways and investigate the expression levels of crucial cancer genes. Melanin biosynthesis genes were solely expressed in the cells of melanocytic origin, indicating the feasibility of using the PET approach for transcriptome comparison. The most significantly altered pathways were metabolic pathways, including upregulated pathways: purine metabolism, aminophosphonate metabolism, tyrosine metabolism, selenoamino acid metabolism, galactose utilization, nitrobenzene degradation, and bisphenol A degradation; and downregulated pathways: oxidative phosphorylation, ATPase synthesis, TCA cycle, pyruvate metabolism, and glutathione metabolism. The downregulated pathways concurrently indicated a slowdown of mitochondrial activities. Mitochondrial permeability was also significantly altered, as indicated by transcriptional activation of ATP/ADP, citrate/malate, Mg++, fatty acid and amino acid transporters, and transcriptional repression of zinc and metal ion transporters. Upregulation of cell cycle progression, MAPK, and PI3K/Akt pathways were more limited to certain region(s) of the pathway. Expression levels

  6. Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes

    Directory of Open Access Journals (Sweden)

    Liu Edison

    2007-06-01

    Full Text Available Abstract Background Melanoma is the major cause of skin cancer deaths and melanoma incidence doubles every 10 to 20 years. However, little is known about melanoma pathway aberrations. Here we applied the robust Gene Identification Signature Paired End diTag (GIS-PET approach to investigate the melanoma transcriptome and characterize the global pathway aberrations. Methods GIS-PET technology directly links 5' mRNA signatures with their corresponding 3' signatures to generate, and then concatenate, PETs for efficient sequencing. We annotated PETs to pathways of KEGG database and compared the murine B16F1 melanoma transcriptome with three non-melanoma murine transcriptomes (Melan-a2 melanocytes, E14 embryonic stem cells, and E17.5 embryo. Gene expression levels as represented by PET counts were compared across melanoma and melanocyte libraries to identify the most significantly altered pathways and investigate the expression levels of crucial cancer genes. Results Melanin biosynthesis genes were solely expressed in the cells of melanocytic origin, indicating the feasibility of using the PET approach for transcriptome comparison. The most significantly altered pathways were metabolic pathways, including upregulated pathways: purine metabolism, aminophosphonate metabolism, tyrosine metabolism, selenoamino acid metabolism, galactose utilization, nitrobenzene degradation, and bisphenol A degradation; and downregulated pathways: oxidative phosphorylation, ATPase synthesis, TCA cycle, pyruvate metabolism, and glutathione metabolism. The downregulated pathways concurrently indicated a slowdown of mitochondrial activities. Mitochondrial permeability was also significantly altered, as indicated by transcriptional activation of ATP/ADP, citrate/malate, Mg++, fatty acid and amino acid transporters, and transcriptional repression of zinc and metal ion transporters. Upregulation of cell cycle progression, MAPK, and PI3K/Akt pathways were more limited to certain

  7. Tool to Distinguish Moles from Melanoma

    Science.gov (United States)

    “Moles to Melanoma: Recognizing the ABCDE Features” presents photos that show changes in individual pigmented lesions over time, and describes the different appearances of moles, dysplastic nevi, and melanomas.

  8. Molecular probes for malignant melanoma imaging.

    Science.gov (United States)

    Ren, Gang; Pan, Ying; Cheng, Zhen

    2010-09-01

    Malignant melanoma represents a serious public health problem and is a deadly disease when it is diagnosed at late stage. Though (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) has been widely used clinically for melanoma imaging, other approaches to specifically identify, characterize, monitor and guide therapeutics for malignant melanoma are still needed. Consequently, many probes targeting general molecular events including metabolism, angiogenesis, hypoxia and apoptosis in melanoma have been successfully developed. Furthermore, probes targeting melanoma associated targets such as melanocortin receptor 1 (MC1R), melanin, etc. have undergone active investigation and have demonstrated high melanoma specificity. In this review, these molecular probes targeting diverse melanoma biomarkers have been summarized. Some of them may eventually contribute to the improvement of personalized management of malignant melanoma. PMID:20497118

  9. Isolated malignant melanoma metastasis to the pancreas

    DEFF Research Database (Denmark)

    Larsen, Anne K; Krag, Christen; Geertsen, Poul;

    2013-01-01

    SUMMARY: Malignant melanomas rarely develop isolated pancreatic metastases. We describe a unique patient who is still alive 22 years following an isolated pancreatic melanoma metastasis, and we review the sparse literature in the field....

  10. Treatment of mouse melanoma cells with phorbol 12-myristate 13-acetate counteracts mannosylerythritol lipid-induced growth arrest and apoptosis.

    Science.gov (United States)

    Zhao, X; Geltinger, C; Kishikawa, S; Ohshima, K; Murata, T; Nomura, N; Nakahara, T; Yokoyama, K K

    2000-07-01

    Mannosylerythritol lipid (MEL), an extracellularglycolipid from yeast, induces the differentiation ofHL-60 promyelocytic leukemia cells towardsgranulocytes. We show here that MEL is also a potentinhibitor of the proliferation of mouse melanoma B16cells. Flow-cytometric analysis of the cell cycle ofMEL-treated B16 cells revealed the accumulation ofcells in the sub-G(0)/G(1) phase, which is a hallmark ofcells undergoing apoptosis. Treatment of B16 cellsfor 24 h with phorbol 12-myristate 13-acetate (PMA),an activator of protein kinase C (PKC), did notinterfere with the growth and survival of the cells,but it effectively counteracted the MEL-induced growtharrest and apoptosis. The activity of PKC was reducedin B16 cells treated with MEL at a concentration atwhich MEL induced apoptosis. However, incubation withPMA in addition to MEL reversed this reduction in theactivity of PKC. These results suggest thatconverging signaling pathways are triggeredindependently by MEL and PMA and that the signalsmight both be mediated by PKC. PMID:19002819

  11. Particularities of melanoma in Romania

    International Nuclear Information System (INIS)

    Full text: Malignant tumor from melanocytic origin, cutaneous melanoma is the most aggressive cutaneous cancer. The particularities of melanoma in Romania are: 1. the increasing number of cases in a geographic area dominated by the third cutaneous phototype; 2. the high level of T, represented by high levels of Breslow and Clark invasion markers; 3. the lack of a National Melanoma Register; 4. the lymph node sentinel biopsy technique introduction is the present focus; this allows an appropriate N affiliation; 5. the increasing of sanitary education in order to clinical and dermoscopical follow-up of atypical moles and the study of risk factors for melanoma; 6. the creation of a melanoma local guide. The survival prognosis could be improved by: a) the early detection in 'in situ' stage of melanoma and b) the correct TNM and/or EORTC affiliation of the case, in order to achieve an appropriate treatment. Sentinel lymph node detection and biopsy offers a new area in the evaluation of cancer spread by detecting micrometastases and performing a complete regional evaluation of the disease. The presence or absence of the metastases in the regional lymph nodes is one of the most important factors in the survival of patients with primary cutaneous melanoma. Early diagnosis of regional lymph node metastases enables the identification of those patients who are candidates for adjuvant therapy and early therapeutic lymph node dissection. At the same time, the sentinel node biopsy procedure represents a sensitive staging method. The paper presents some of gold standard diagnosis cases, dermoscopy and routine HE examination, selected from a total of 356 cases. (author)

  12. Novel photosensitizers trigger rapid death of malignant human cells and rodent tumor transplants via lipid photodamage and membrane permeabilization.

    Directory of Open Access Journals (Sweden)

    Mikhail M Moisenovich

    Full Text Available BACKGROUND: Apoptotic cascades may frequently be impaired in tumor cells; therefore, the approaches to circumvent these obstacles emerge as important therapeutic modalities. METHODOLOGY/PRINCIPAL FINDINGS: Our novel derivatives of chlorin e(6, that is, its amide (compound 2 and boronated amide (compound 5 evoked no dark toxicity and demonstrated a significantly higher photosensitizing efficacy than chlorin e(6 against transplanted aggressive tumors such as B16 melanoma and M-1 sarcoma. Compound 5 showed superior therapeutic potency. Illumination with red light of mammalian tumor cells loaded with 0.1 µM of 5 caused rapid (within the initial minutes necrosis as determined by propidium iodide staining. The laser confocal microscopy-assisted analysis of cell death revealed the following order of events: prior to illumination, 5 accumulated in Golgi cysternae, endoplasmic reticulum and in some (but not all lysosomes. In response to light, the reactive oxygen species burst was concomitant with the drop of mitochondrial transmembrane electric potential, the dramatic changes of mitochondrial shape and the loss of integrity of mitochondria and lysosomes. Within 3-4 min post illumination, the plasma membrane became permeable for propidium iodide. Compounds 2 and 5 were one order of magnitude more potent than chlorin e(6 in photodamage of artificial liposomes monitored in a dye release assay. The latter effect depended on the content of non-saturated lipids; in liposomes consisting of saturated lipids no photodamage was detectable. The increased therapeutic efficacy of 5 compared with 2 was attributed to a striking difference in the ability of these photosensitizers to permeate through hydrophobic membrane interior as evidenced by measurements of voltage jump-induced relaxation of transmembrane current on planar lipid bilayers. CONCLUSIONS/SIGNIFICANCE: The multimembrane photodestruction and cell necrosis induced by photoactivation of 2 and 5 are

  13. Transplant Process

    Science.gov (United States)

    ... typing, including high-resolution typing A complete health history and physical exam Evaluation of your psychological and emotional strengths Identifying who will be your primary caregiver throughout the transplant process Bone marrow biopsy CT (computed tomography) scan or MRI (magnetic ...

  14. Kidney Transplant

    Science.gov (United States)

    ... You are here Home » Kidney Transplant Click to watch a video on this topic Click to watch a video on Hemodialysis When kidneys fail, there ... 05/2016 - 10:00am Philadelphia, PA Kidney Camp Sun, 07/17/2016 - 6:00pm Ingleside, IL Register ...

  15. Heart Transplantation

    Science.gov (United States)

    A heart transplant removes a damaged or diseased heart and replaces it with a healthy one. The healthy heart comes from a donor who has died. It is the last resort for people with heart failure when all other treatments have failed. The ...

  16. In vivo overexpression of tumstatin domains by tumor cells inhibits their invasive properties in a mouse melanoma model

    International Nuclear Information System (INIS)

    Our previous studies demonstrated that a synthetic peptide encompassing residues 185-203 of the noncollagenous (NC1) domain of the α3 chain of type IV collagen, named tumstatin, inhibits in vitro melanoma cell proliferation and migration. In the present study, B16F1 melanoma cells were stably transfected to overexpress the complete tumstatin domain (Tum 1-232) or its C-terminal part, encompassing residues 185-203 (Tum 183-232). Tumstatin domain overexpression inhibited B16F1 in vitro cell proliferation, anchorage-independent growth, and invasive properties. For studying the in vivo effect of overexpression, representative clones were subcutaneously injected into the left side of C57BL6 mice. In vivo tumor growth was decreased by -60% and -56%, respectively, with B16F1 cells overexpressing Tum 1-232 or Tum 183-232 compared to control cells. This inhibitory effect was associated with a decrease of in vivo cyclin D1 expression. We also demonstrated that the overexpression of Tum 1-232 or Tum 183-232 induced an in vivo down-regulation of proteolytic cascades involving matrix metalloproteinases (MMPs), especially the production or activation of MMP-2, MMP-9, MMP-13, as well as MMP-14. The plasminogen activation system was also altered in tumors with a decrease of urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) and a strong increase of plasminogen activator inhibitor-1 (PAI-1). Collectively, our results demonstrate that tumstatin or its C-terminal antitumor fragment, Tum 183-232, inhibits in vivo melanoma progression by triggering an intracellular transduction pathway, which involves a cyclic AMP (cAMP)-dependent mechanism

  17. Melanoma vaccines: trials and tribulations

    Directory of Open Access Journals (Sweden)

    Dillman RO

    2013-10-01

    Full Text Available Robert O Dillman1,21Hoag Cancer Institute and Hoag Institute for Research and Education, Newport Beach, CA, USA; 2University of California Irvine, Irvine, CA, USAAbstract: Metastatic melanoma has been a target of immunotherapy for more than 4 decades. Three immunotherapeutics have received regulatory approval for treating melanoma: interferon-alpha, interleukin-2, and ipilimumab. The antitumor mechanisms of these products depend on enhancing existing immune responses, including autoimmune effects. The combination of autologous, cytotoxic T-lymphocytes plus high-dose interleukin-2 is a promising patient-specific therapy, but has limited clinical application. Other approaches include vaccines targeting melanoma-associated antigens, and patient-specific vaccines that utilize autologous tumor. Non-patient-specific vaccine approaches target melanocyte differentiation antigens (eg, tyrosinase, Melan-A, gp100, antigens identified by cytotoxic T-lymphocytes (eg, NY-Eso-1, Melan-A/Mart-1, Mage-3, and antigens originally identified by murine monoclonal antibodies (gangliosides, gp97, gp225. Self-renewing cells in tumor cell lines may represent tumor stem cells, but vaccines derived from allogeneic tumor cell lines have yielded disappointing results in randomized trials. Patient-specific vaccines can be derived from bulk autologous tumor or autologous tumor cell lines, and intratumoral injections of immunostimulatory fusion products have shown promise. While technically more complex to manufacture, patient-specific vaccines derived from autologous tumor cell lines have the potential to target tumor stem cells and overcome interpatient tumor cell heterogeneity. This article reviews sources of melanoma-associated antigens, costimulatory agents, and clinical trial results for various melanoma vaccines. Comparing Phase II trials is difficult because of the wide range of vaccine strategies and the differences in study patient populations; therefore, randomized

  18. Design of Pluronic-Based Formulation for Enhanced Redaporfin-Photodynamic Therapy against Pigmented Melanoma.

    Science.gov (United States)

    Pucelik, Barbara; Arnaut, Luis G; Stochel, Grażyna; Dąbrowski, Janusz M

    2016-08-31

    The therapeutic outcome of photodynamic therapy (PDT) with redaporfin (a fluorinated sulfonamide bacteriochlorin, F2BMet or LUZ11) was improved using Pluronic-based (P123, F127) formulations. Neither redaporfin encapsulated in Pluronic nor micelles alone exhibited cytotoxicity in a broad concentration range. Comprehensive in vitro studies against B16F10 melanoma cells showed that redaporfin-P123 micelles enhanced cellular uptake and increased oxidative stress compared with redaporfin-F127 or photosensitizer alone after short incubation times. ROS-sensitive fluorescent probes showed that the increased oxidative stress is due, at least in part, to a more efficient formation of hydroxyl radicals, and causes strong light-dose dependent apoptosis and necrosis. Tissue distribution and pharmacokinetic studies in tumor-bearing mice show that the Pluronic P123 formulation of redaporfin increases its bioavailability as well as the tumor-to-muscle and tumor-to-skin ratios, in comparison with Cremophor EL and Pluronic F127 formulations. Redaporfin in P123 was most successful in the PDT of C57BL/6J mice bearing subcutaneously implanted B16F10 melanoma tumors. Vascular-targeted PDT combining 1.5 mg kg(-1) redaporfin in P123 with a light dose of 74 J cm(-2) led to 100% complete cures (i.e., no tumor regrowth over one year post-treatment). This remarkable result reveals that modification of redaporfin with Pluronic block copolymers overcomes the resistance of melanoma cells to PDT possibly via increased tumor selectivity and enhanced ROS generation. PMID:27492026

  19. Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

    International Nuclear Information System (INIS)

    Introduction: In spite of recently approved B-RAF inhibitors and immunomodulating antibodies, metastatic melanoma has poor prognosis and novel treatments are needed. Melanoma stem cells (MSC) have been implicated in the resistance of this tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in patients with metastatic melanoma that radioimmunotherapy (RIT) with 188-Rhenium(188Re)-6D2 antibody to melanin was a safe and effective modality. Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy. Methods: Mice bearing A2058 melanoma xenografts were treated with either 1.5 mCi 188Re-6D2 antibody, saline, unlabeled 6D2 antibody or 188Re-labeled non-specific IgM. Results: On Day 28 post-treatment the tumor size in the RIT group was 4-times less than in controls (P < 0.001). The tumors were analyzed by immunohistochemistry and FACS for two MSC markers — chemoresistance mediator ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the tumor population. Our results demonstrate that unlike chemotherapy, which kills tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the same rate as the rest of tumor cells. Conclusions: These results have two main implications for melanoma treatment and possibly other cancers. First, the susceptibility of ABCB5 + and JARID1B + cells to RIT in melanoma might be indicative of their susceptibility to antibody-targeted radiation in other cancers where they are present as well. Second, specifically targeting cancer stem cells with radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate cancer stem cells in various cancers

  20. CDX-1401 and Poly-ICLC Vaccine Therapy With or Without CDX-301in Treating Patients With Stage IIB-IV Melanoma

    Science.gov (United States)

    2016-06-21

    Carcinoma of Unknown Primary Origin; Iris Melanoma; Medium/Large Size Posterior Uveal Melanoma; Mucosal Melanoma; Ocular Melanoma With Extraocular Extension; Small Size Posterior Uveal Melanoma; Stage IIB Skin Melanoma; Stage IIB Uveal Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIA Uveal Melanoma; Stage IIIB Skin Melanoma; Stage IIIB Uveal Melanoma; Stage IIIC Skin Melanoma; Stage IIIC Uveal Melanoma; Stage IV Skin Melanoma; Stage IV Uveal Melanoma

  1. Resveratrol prevents inflammation-dependent hepatic melanoma metastasis by inhibiting the secretion and effects of interleukin-18

    Directory of Open Access Journals (Sweden)

    Valcarcel Maria

    2011-05-01

    Full Text Available Abstract Background Implantation and growth of metastatic cancer cells at distant organs is promoted by inflammation-dependent mechanisms. A hepatic melanoma metastasis model where a majority of metastases are generated via interleukin-18-dependent mechanisms was used to test whether anti-inflammatory properties of resveratrol can interfere with mechanisms of metastasis. Methods Two experimental treatment schedules were used: 1 Mice received one daily oral dose of 1 mg/kg resveratrol after cancer cell injection and the metastasis number and volume were determined on day 12. 2 Mice received one daily oral dose of 1 mg/kg resveratrol along the 5 days prior to the injection of cancer cells and both interleukin-18 (IL-18 concentration in the hepatic blood and microvascular retention of luciferase-transfected B16M cells were determined on the 18th hour. In vitro, primary cultured hepatic sinusoidal endothelial cells were treated with B16M-conditioned medium to mimic their in vivo activation by tumor-derived factors and the effect of resveratrol on IL-18 secretion, on vascular cell adhesion molecule-1 (VCAM-1 expression and on tumor cell adhesion were studied. The effect of resveratrol on melanoma cell activation by IL-18 was also studied. Results Resveratrol remarkably inhibited hepatic retention and metastatic growth of melanoma cells by 50% and 75%, respectively. The mechanism involved IL-18 blockade at three levels: First, resveratrol prevented IL-18 augmentation in the blood of melanoma cell-infiltrated livers. Second, resveratrol inhibited IL-18-dependent expression of VCAM-1 by tumor-activated hepatic sinusoidal endothelium, preventing melanoma cell adhesion to the microvasculature. Third, resveratrol inhibited adhesion- and proliferation-stimulating effects of IL-18 on metastatic melanoma cells through hydrogen peroxide-dependent nuclear factor-kappaB translocation blockade on these cells. Conclusions These results demonstrate multiple sites

  2. ORAL MELANOMA: A FATAL ENTITY

    Directory of Open Access Journals (Sweden)

    Amit

    2014-08-01

    Full Text Available : Oral melanomas are uncommon and similar to their cutaneous counterparts, are neoplasm that developed from melanocytic cells lying in the basal layer of the mucosa, its incidence is about 1.2 cases per 10 million inhabitants per year with a variation between 0.2% to 8% of all the melanomas and 0.5% of all the malignant neoplasias of the oral cavity.1 Oral conditions with increased melanin pigmentation are common; however, melanocytic hyperplasias are rare. The relative incidence amongst mucosal neoplasms of the head and neck had been reviewed by Hormia and Vuori2, about 7253 cases of malignancies of upper respiratory and gastrointestinal tracts between 1953-1964, five cases of oral melanoma were found with an incidence of 0.07%

  3. Prognostic stratification of ulcerated melanoma

    DEFF Research Database (Denmark)

    Bønnelykke-Behrndtz, Marie L; Schmidt, Henrik; Christensen, Ib J; Damsgaard, Tine E; Møller, Holger J; Bastholt, Lars; Nørgaard, Peter H; Steiniche, Torben

    2014-01-01

    OBJECTIVES: For patients with melanoma, ulceration is an important prognostic marker and interestingly also a predictive marker for the response of adjuvant interferon. A consensual definition and accurate assessment of ulceration are therefore crucial for proper staging and clinical management. We...... stratification of ulcerated lesions. METHODS: From H&E-stained sections, the status (presence vs absence), extent (percentage of the total tumor length), and type (infiltrative vs attenuative) of ulceration and epidermal involvement were evaluated from 385 patients with cutaneous melanoma. RESULTS: The presence...... of ulceration (hazard ratio [HR], 1.83), an attenuative type of ulceration (HR, 3.02), and excessive ulceration (HR, 3.57) were independent predictors of poor melanoma-specific survival. Further subdivision of minimal/moderate ulceration showed independent prognostic value only for lesions with...

  4. Genetic alterations and markers of melanoma

    Directory of Open Access Journals (Sweden)

    N. N. Mazurenko

    2014-01-01

    Full Text Available Melanoma remains the most deadly form of malignant skin disease with high risk of metastases. Metastatic melanoma is prognostic highly unfavorable and resistant to traditional chemotherapy and biologic treatment. There is a great progress in understanding of the molecular mechanisms underlying melanoma initiation and progression. The external (ultraviolet irradiation and internal (genetic factors are involved in melanoma genesis. 5–14 % of melanoma cases occur in familial context due to genetic predisposition risk factors. Among them rare germinal mutations in the cell cycle genes regulators CDKN2A and CDK4 and in the master gene of melanocyte homeostasis MITF, as well as single nucleotide polymorphisms of several low-penetrated genes, namely MC1R, have been identified. The main cell signaling pathways and oncogene driver mutations are involved in melanoma pathogenesis. RAS / RAF / MEK / ERK cascade is hyperactivated in 75 % of cutaneous melanoma cases. Activation of PI3K / AKT / mTOR signaling pathway is important for melanoma progression. Recent studies revealed that melanomas are genetically and phenotypically heterogeneous tumors. Spectrum of chromosomal alterations and activating mutations corresponding to tumor molecular portraits varies in melanomas of different location. Most of cutaneous melanomas contain BRAF (50 % or NRAS (20 % mutations, and NRAS mutations occur on chronically sun-exposed skin. Activating KIT mutations have been reported in approximately 20–30 % of certain subtypes of melanoma, including acral and mucosal, and melanoma that develop on photodamaged skin. Cutaneous metastatic melanoma derive from preexisting nevi in 25 % of cases, molecular mechanisms of nevi malignization are discussed. Deepsequencing approaches of melanoma samples of different melanoma types highlighted new melanoma driver genes, that are damaged due to tumorigenic effects of ultraviolet: PPP6C, RAC1, SNX31, TACC1 and STK19. The

  5. Recombinant snake venom metalloproteinase inhibitor BJ46A inhibits invasion and metastasis of B16F10 and MHCC97H cells through reductions of matrix metalloproteinases 2 and 9 activities.

    Science.gov (United States)

    Ji, Ming-Kai; Shi, Yi; Xu, Jian-Wen; Lin, Xu; Lin, Jian-Yin

    2013-06-01

    Studies have shown that the recombinant BJ46a (rBJ46a) protein can reduce matrix metalloproteinase (MMP) activities and inhibit invasion and metastasis of melanoma cells. Here, we optimized the Pichia pastoris system to evaluate rBJ46a protein as an anticancer agent. The Enzchek gelatinase/collagenase assay showed that rBJ46a inhibited MMP activities (IC50=0.119 mg/ml). Kinetic analyses using a series of double reciprocal Lineweaver-Burk plots (1/V vs. 1/S) showed a competitive mode of inhibition with rBJ46a with inhibitory efficiency against MMPs (Ki=13.6 nmol/l). Matrigel invasion assays showed significant activity of rBJ46a on tumor cells. For lung colonization assays, C57BL/6 mice were inoculated in the lateral tail vein with B16F10 cells and were treated with three i.v. injections of rBJ46a (1, 2, and 4 mg/kg) 24 h before cell inoculation, and 2 and 24 h after cell inoculation. Administration of rBJ46a suppressed lung tumor colony formation significantly. For spontaneous metastasis assays, MHCC97H cells were inoculated subcutaneously into nude mice. After 24 h, rBJ46a was administered by i.p. injections: 1, 2, and 4 mg/kg once daily for 6 days. rBJ46a decreased lung tumor colony formation significantly. Gelatin zymography showed that MMP2/MMP9 enzymatic activities in tumor cells were suppressed by rBJ46a in a dose-dependent manner, and the Km values of rBJ46a against MMP2 and MMP9 activities that were expressed in both B16F10 and MHCC97H cells were 3.6 and 1.4 μmol/l, respectively. Thus, rBJ46a can inhibit the invasion and metastasis of tumor cells by reducing MMP2/MMP9 activities, indicating that rBJ46a may be a novel therapeutic agent for antimetastasis of tumor cells. PMID:23442578

  6. YAG laser induced hyperthermia as an adjunctive treatment for ocular melanoma

    International Nuclear Information System (INIS)

    The correct treatment for choroidal melanoma is under debate, but radiation therapy (scleral plaques or external beam charged particles) is being used as the primary therapy in an increasing number of patients. Secondary effects of ocular radiation therapy are observed several years after treatment and can result in a significant decrease in visual acuity. Adjunctive use of ocular hyperthermia could reduce the dose of ionizing radiation needed to sterilize choroidal melanoma. In addition, if the production of ocular hyperthermia can be limited only to the tumor, then a reduction in the dose of ocular radiation could in turn reduce the severity of secondary complications to normal ocular structures. The authors performed preclinical studies with a low power continuous wave YAG laser as a source of precise and efficient hyperthermia. Tumor temperature profiles have been determined as a function of laser light power density and tumor function of laser light power density and tumor tissue depth in mice with B-16 melanomas. Ocular toxicity (in and out of the treatment field) induced by YAG laser hyperthermia has also been examined in pigmented rabbits using fundus photography, fluorrescein angiography and histopathology. Their results suggest that the YAG laser can generate efficient and highly localized hyperthermia, and may be useful in treating ocular tumors

  7. Encapsulation of palladium porphyrin photosensitizer in layered metal oxide nanoparticles for photodynamic therapy against skin melanoma

    Science.gov (United States)

    Chen, Zih-An; Kuthati, Yaswanth; Kankala, Ranjith Kumar; Chang, Yu-Chuan; Liu, Chen-Lun; Weng, Ching-Feng; Mou, Chung-Yuan; Lee, Chia-Hung

    2015-10-01

    We designed a biodegradable nanocarrier of layered double hydroxide (LDH) for photodynamic therapy (PDT) based on the intercalation of a palladium porphyrin photosensitizer (PdTCPP) in the gallery of LDH for melanoma theragnosis. Physical and chemical characterizations have demonstrated the photosensitizer was stable in the layered structures. In addition, the synthesized nanocomposites rendered extremely efficacious therapy in the B16F10 melanoma cell line by improving the solubility of the hydrophobic PdTCPP photosensitizer. The detection of singlet oxygen generation under irradiation at the excitation wavelength of a 532 nm laser was indeed impressive. Furthermore, the in vivo results using a tumour xenograft model in mice indicated the apparent absence of body weight loss and relative organ weight variation to the liver and kidney demonstrated that the nanocomposites were biosafe with a significant reduction in tumour volume for the anti-cancer efficacy of PDT. This drug delivery system using the nanoparticle-photosensitizer hybrid has great potential in melanoma theragnosis.

  8. Semaphorin 3A suppresses tumor growth and metastasis in mice melanoma model.

    Directory of Open Access Journals (Sweden)

    Goutam Chakraborty

    Full Text Available BACKGROUND: Recent understanding on cancer therapy indicated that targeting metastatic signature or angiogenic switch could be a promising and rational approach to combat cancer. Advancement in cancer research has demonstrated the potential role of various tumor suppressor proteins in inhibition of cancer progression. Current studies have shown that axonal sprouting inhibitor, semaphorin 3A (Sema 3A acts as a potent suppressor of tumor angiogenesis in various cancer models. However, the function of Sema 3A in regulation of melanoma progression is not well studied, and yet to be the subject of intense investigation. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using multiple in vitro and in vivo approaches we have demonstrated that Sema 3A acts as a potent tumor suppressor in vitro and in vivo mice (C57BL/6 models. Mouse melanoma (B16F10 cells overexpressed with Sema 3A resulted in significant inhibition of cell motility, invasiveness and proliferation as well as suppression of in vivo tumor growth, angiogenesis and metastasis in mice models. Moreover, we have observed that Sema 3A overexpressed melanoma clone showed increased sensitivity towards curcumin and Dacarbazine, anti-cancer agents. CONCLUSIONS: Our results demonstrate, at least in part, the functional approach underlying Sema 3A mediated inhibition of tumorigenesis and angiogenesis and a clear understanding of such a process may facilitate the development of novel therapeutic strategy for the treatment of cancer.

  9. Inhibitory Effects of Far-Infrared Irradiation Generated by Ceramic Material on Murine Melanoma Cell Growth

    Directory of Open Access Journals (Sweden)

    Ting-Kai Leung

    2012-01-01

    Full Text Available The biological effects of specific wavelengths, so-called “far-infrared radiation” produced from ceramic material (cFIR, on whole organisms are not yet well understood. In this study, we investigated the biological effects of cFIR on murine melanoma cells (B16-F10 at body temperature. cFIR irradiation treatment for 48 h resulted in an 11.8% decrease in the proliferation of melanoma cells relative to the control. Meanwhile, incubation of cells with cFIR for 48 h significantly resulted in 56.9% and 15.7% decreases in the intracellular heat shock protein (HSP70 and intracellular nitric oxide (iNO contents, respectively. Furthermore, cFIR treatment induced 6.4% and 12.3% increases in intracellular reactive oxygen species stained by 5-(and 6-carboxyl-2′,7′-dichlorodihydrofluorescein diacetate and dihydrorhodamine 123, respectively. Since malignant melanomas are known to have high HSP70 expression and iNO activity, the suppressive effects of cFIR on HSP70 and NO may warrant future interest in antitumor applications.

  10. Pancreas Transplantation

    OpenAIRE

    Han, Duck Jong; Sutherland, David ER

    2010-01-01

    Diabetes mellitus is generally treated with oral diabetic drugs and/or insulin. However, the morbidity and mortality associated with this condition increases over time, even in patients receiving intensive insulin treatment, and this is largely attributable to diabetic complications or the insulin therapy itself. Pancreas transplantation in humans was first conducted in 1966, since when there has been much debate regarding the legitimacy of this procedure. Technical refinements and the develo...

  11. Transplant Center Search Form

    Science.gov (United States)

    ... Your Story Give Us Feedback - A + A Transplant Center Search Form Welcome to the Blood & Marrow Transplant ... centers for patients with a particular disease. Transplant Center login Username: * Password: * Request new password Join BMT ...

  12. Melanoma imaging using 111In-, 86Y- and 68Ga-labeled CHX-A''-Re(Arg11)CCMSH

    International Nuclear Information System (INIS)

    Introduction: A novel alpha-melanocyte-stimulating hormone peptide analog CHX-A''-Re(Arg11)CCMSH, which targeted the melanocortin-1 receptor (MC1-R) overexpressed on melanoma cells, was investigated for its biodistribution and tumor imaging properties. Methods: The metal bifunctional chelator CHX-A'' was conjugated to the melanoma targeting peptide (Arg11)CCMSH and cyclized by Re incorporation to yield CHX-A''-Re(Arg11)CCMSH. CHX-A''-Re(Arg11)CCMSH was labeled with 111In, 86Y and 68Ga, and the radiolabeled peptides were examined in B16/F1 melanoma-bearing mice for their pharmacokinetic as well as their tumor targeting properties using small animal SPECT and PET. Results: The radiolabeling efficiencies of the 111In-, 86Y- and 68Ga-labeled CHX-A''-Re(Arg11)CCMSH peptides were >95%, resulting in specific activities of 4.44, 3.7 and 1.85 MBq/μg, respectively. Tumor uptake of the 111In-, 86Y- and 68Ga-labeled peptides was rapid with 4.17±0.94, 4.68±1.02 and 2.68±0.69 %ID/g present in the tumors 2 h postinjection, respectively. Disappearance of radioactivity from the normal organs and tissues was rapid with the exception of the kidneys. Melanoma tumors were imaged with all three radiolabeled peptides 2 h postinjection. MC1-R-specific uptake was confirmed by competitive receptor blocking studies. Conclusions: Melanoma tumor uptake and imaging was exhibited by the 111In-, 86Y- and 68Ga-labeled Re(Arg11)CCMSH peptides, although the tumor uptake was moderated by low specific activity. The facile radiolabeling properties of CHX-A''-Re(Arg11)CCMSH allow it to be employed as a melanoma imaging agent with little or no purification after 111In, 86Y and 68Ga labeling.

  13. The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis

    International Nuclear Information System (INIS)

    Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid (EACA) and plg-/- mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg-/- less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain

  14. How Transplant Can Treat ALD

    Science.gov (United States)

    ... to 20-year friendship Supporter stories Valerie Sun - bone marrow transplant patient advocate Jeff and Kim take their life- ... transplant and other treatment options What is a bone marrow transplant How a bone marrow transplant works Transplant process ...

  15. Experimental stress analysis and fatigue tests of five 24-in. NPS ANSI Standard B16.9 tees

    International Nuclear Information System (INIS)

    Experimental stress analyses and low-cycle fatigue tests of five 24-in. nominal pipe size American National Standards Institute (ANSI) Standard B16.9 forged tees are documented in this report. The tees, designated as Oak Ridge National Laboratory tees T10, T11, T12, T13, and T16, were tested under subcontract at Combustion Engineering, Inc. in Chattanooga, Tennessee. Experimental stress analyses were conducted for 12 individual loadings on each tee. Each test model was instrumented with approx. 225, 1/8-in. three-gage, 450 strain rosettes on the inside and outside surfaces; and 6 linear variable differential transformers mounted on special nonflexible holding frames for measuring deflections and rotations of the pipe extensions. Following completion of the strain-gate tests, each tee was fatigue tested to failure with either a fully reversed displacement controlled in-plane bending moment on the branch or a cyclic internal pressure that ranged from a value slightly above zero to about 90% of the nominal yield pressure of the pipe extensions

  16. trans-[Ru(NO)Cl(cyclam)](PF6)2 and [Ru(NO)(Hedta)] incorporated in PLGA nanoparticles for the delivery of nitric oxide to B16-F10 cells: cytotoxicity and phototoxicity.

    Science.gov (United States)

    Gomes, Anderson J; Espreafico, Enilza M; Tfouni, Elia

    2013-10-01

    The immobilization and characterization of trans-[Ru(NO)Cl(cyclam)](PF6)2 (cyclam=1,4,8,11-tetraazacyclotetradecane), and [Ru(NO)(Hedta)] (Hedta=ethylenediaminetetraacetic acid) entrapped in poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles (NP) using the double emulsification process is described. Scanning electron microscopy and dynamic light scattering revealed that the particles are spherical in shape, have a size distribution between 220 and 840 nm of diameter, and have a tendency to aggregate confirmed by a zeta potential between -3.2 and +3.5 mV. Using this method the loading efficiency was 26% for trans-[Ru(NO)Cl(cyclam)](PF6)2 and 32% for [Ru(NO)(Hedta)]. The release of the complexes from the NPs shows that cyclam-NP and Hedta-NP exhibited a two-phase exponential association release pattern, which was characterized by an initial complex burst during the first 24 h, followed by a slower release phase complex profile, due to a few pores observed in surface of nanoparticles using atomic force microscopy. The in vitro cytotoxic activity of the nitrosyl complexes in solution and incorporated in PLGA nanoparticles on melanoma cancer cells (cell line B16-F10) was investigated. The lower cytotoxicity of trans-[RuCl(cyclam)(NO)]2+ (12.4±2.6%) and [Ru(NO)(Hedta)] (4.0±2.7%) in solution compared to that of trans-[Ru(NO)(NH3)4py]3+ (46.1±6.4%) is consistent with the rate constant release of NO of these complexes (k-NO=6.2×10(-4) s(-1), 2.0×10(-3) s(-1), and 6.0×10(-2) s(-1), respectively); the cytotoxicities are also inhibited in the presence of the NO scavenger carboxy-PTIO. The phototoxicity of these complexes is due to NO release, which lead to 53.8±6.2% of cell death in the presence of trans-[Ru(NO)Cl(cyclam)](PF6)2 and 22.3±5.1% in the presence of [Ru(NO)(Hedta)]. The PLGA nanoparticles loaded with trans-[Ru(NO)Cl(cyclam)](PF6)2 and [Ru(NO)(Hedta)] exerted in vitro a reduced activity against melanoma cells when compared to the activity of complex in

  17. Tumor Heterogeneity in Uveal Melanomas

    NARCIS (Netherlands)

    H.W. Mensink (Hanneke)

    2010-01-01

    textabstractUveal melanoma (UM) is the most common primary intraocular malignancy in adults with an incidence of 7-10/ million and has a predilection for hematogenous dissemination to the liver. Despite improvements in diagnosis and treatment of this intraocular tumor, there has not been a change in

  18. Biology of Human Cutaneous Melanoma

    OpenAIRE

    Sharma, Bhuvnesh K.; Hasskamp, Joanne H.; Elias, Elias G.

    2010-01-01

    A review of the natural behavior of cutaneous melanoma, clinical and pathological factors, prognostic indicators, some basic research and the present and possible futuristic strategies in the management of this disease are presented. While surgery remains to be the most effective therapeutic approach in the management of early primary lesions, there is no standard adjuvant therapy after surgical resection, or for metastatic disease.

  19. [Endocrine factors influencing melanoma progression].

    Science.gov (United States)

    Dobos, Judit

    2009-03-01

    According to recent findings that beside cancers traditionally considered as hormone-dependent, several other tumor types show different behavior in the two sexes, indicating the possible role of endocrine factors in the course of these diseases. The possibility that endocrine factors may influence the clinical course of human malignant melanoma is suggested by the higher survival rate in premenopausal vs. postmenopausal women or men of any ages. However, investigations on the sex hormone receptor status of human cutaneous melanomas and experiments attempting to support the epidemiological results yielded conflicting results. In our human melanoma cell lines we failed to detect steroid receptors at protein level, while quantitative PCR demonstrated that their mRNA expression level was orders of magnitude lower compared to the positive control cell lines. Sex hormones did not influence the in vitro features of the human melanoma cells considerably. On the other hand, glucocorticoid receptor was present both at mRNA and protein level, although dexamethasone was effective in vitro only at high doses. Our previous experiments showed that intrasplenic injection of human melanoma cells resulted in a significantly higher number of liver colonies in male than in female SCID mice. We now show that this difference evolves during the first day. After injection into the tail vein we did not observe gender-dependent difference in the efficiency of pulmonary colonization. Examining the pattern of metastasis formation after intracardiac injection, we have found differences between the two sexes in the incidence or number of colonies only in the case of the liver but not in other organs. We concluded that the observed phenomenon is specific to the liver; therefore we investigated the effects of 2-methoxyestradiol, an endogenous metabolite of estradiol produced mainly in the liver, with an estrogen receptor-independent antitumor activity. 2ME2 effectively inhibited melanoma cell

  20. Cu-64-labeled lactam bridge-cyclized α-MSH peptides for PET imaging of melanoma.

    Science.gov (United States)

    Guo, Haixun; Miao, Yubin

    2012-08-01

    The purpose of this study was to examine and compare the melanoma targeting and imaging properties of (64)Cu-NOTA-GGNle-CycMSH(hex) {(64)Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} and (64)Cu-DOTA-GGNle-CycMSH(hex) {(64)Cu-1,4,7,10-tetraazacyclononane-1,4,7,10-tetraacetic acid-GGNle-CycMSH(hex)}. Two lactam bridge-cyclized peptides, NOTA-GGNle-CycMSH(hex) and DOTA-GGNle-CycMSH(hex), were synthesized using fluorenylmethyloxy carbonyl (Fmoc) chemistry. The melanocortin-1 (MC1) receptor binding affinity of NOTA-GGNle-CycMSH(hex) was determined in B16/F1 melanoma cells and compared with DOTA-GGNle-CycMSH(hex). The melanoma targeting and imaging properties of (64)Cu-NOTA-GGNle-CycMSH(hex) and (64)Cu-DOTA-GGNle-CycMSH(hex) were determined in B16/F1 melanoma-bearing C57 mice. NOTA-GGNle-CycMSH(hex) and DOTA-GGNle-CycMSH(hex) displayed comparable MC1 receptor binding affinities (1.6 vs 2.1 nM). The substitution of DOTA with NOTA dramatically increased the melanoma uptake and decreased the renal and liver uptake of (64)Cu-NOTA-GGNle-CycMSH(hex). The tumor uptake of (64)Cu-NOTA-GGNle-CycMSH(hex) was between 12.39 ± 1.61 and 12.71 ± 2.68% ID/g at 0.5, 2, and 4 h postinjection. The accumulation of (64)Cu-NOTA-GGNle-CycMSH(hex) activity in normal organs was lower than 1.02% ID/g except for the kidneys 2, 4, and 24 h postinjection. The tumor/liver uptake ratios of (64)Cu-NOTA-GGNle-CycMSHhex were 17.96, 16.95, and 8.02, whereas the tumor/kidney uptake ratios of (64)Cu-NOTA-GGNle-CycMSH(hex) were 2.52, 3.60, and 5.74 at 2, 4, and 24 h postinjection, respectively. Greater than 91% of the injected radioactivity cleared through the urinary system by 2 h postinjection. The substitution of DOTA with NOTA resulted in a dramatic increase in melanoma uptake and decrease in renal and liver uptake of (64)Cu-NOTA-GGNle-CycMSH(hex) as compared to (64)Cu-DOTA-GGNle-CycMSH(hex). High melanoma uptake coupled with low accumulation in nontarget